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Trevisan A, de Araujo-Souza PS, Pincivy A, Niyibizi J, Franco EL, Trottier H. Systematic review and meta-analysis of the association between naturally induced IgG, IgM and neutralising antibodies to HPV16 and newly detected cervical HPV16 infection outcomes. Sex Transm Infect 2025; 101:191-199. [PMID: 39542714 DOI: 10.1136/sextrans-2024-056296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 10/22/2024] [Indexed: 11/17/2024] Open
Abstract
BACKGROUND It is unclear whether recurrent cervical human papillomavirus type 16 (HPV16) infections can be prevented by naturally induced HPV16 antibodies in unvaccinated healthy women. METHODS We systematically searched the literature for studies that prospectively evaluated the association between HPV16 naturally induced IgG, IgM, and neutralising antibodies and newly detected cervical HPV16 infection in unvaccinated women. Data were quantitatively summarised by random effect meta-analysis. RESULTS Naturally induced HPV16 IgG and neutralising antibodies were negatively associated with newly detected HPV16 infection (relative risk (RR) (95% confidence interval (CI))=0.71 (0.63 to 0.80) and 0.54 (0.36 to 0.73), respectively). HPV16 antibodies tend to offer protection against subsequent HPV16 DNA detection in young women (RR (95% CI)=0.65 (0.55 to 0.74)), but not in women aged over 25 years (RR (95% CI)=0.88 (0.73 to 1.04)). HPV16 IgG antibodies were also negatively associated with persistent HPV16 infection (adjusted RR=0.67 (0.56 to 0.78)). There was high heterogeneity between studies (I2 statistic=63.9%; p=0.007), and most had low risk of bias. We did not find studies evaluating IgM antibodies. CONCLUSION Seroreactivity to HPV16 infection seems to provide moderate protection against newly detected cervical HPV16 infection outcomes in unvaccinated women. However, protection seems to be affected by age. These findings should be considered when evaluating public health interventions against HPV. PROSPERO REGISTRATION NUMBER CRD42022339579.
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Affiliation(s)
- Andrea Trevisan
- Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Montreal, Quebec, Canada
- Sainte-Justine Hospital Research Center, Université de Montréal, Montreal, Quebec, Canada
| | | | - Alix Pincivy
- Sainte-Justine Hospital Research Center, Université de Montréal, Montreal, Quebec, Canada
| | - Joseph Niyibizi
- Sainte-Justine Hospital Research Center, Université de Montréal, Montreal, Quebec, Canada
| | - Eduardo L Franco
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
| | - Helen Trottier
- Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Montreal, Quebec, Canada
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2
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Park EY, Minkner R. A systematic approach for scalable purification of virus-like particles. Protein Expr Purif 2025; 228:106664. [PMID: 39828016 DOI: 10.1016/j.pep.2025.106664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 01/13/2025] [Accepted: 01/16/2025] [Indexed: 01/22/2025]
Abstract
Virus-like particles (VLPs) are increasingly recognized as promising vaccine candidates and drug-delivery platforms because they do not contain genetic materials, mimic viral structures, and possess strong antigenic properties. Various hosts, including microorganisms, yeast, and insect cells, are commonly used for VLP expression. Recently, silkworms have emerged as a significant host for producing VLPs, providing a cost-effective and straightforward approach for large-scale expression. Despite the progress in VLP expression technology, purification methods for VLPs are still in their infancy and often rely on unscalable ultracentrifugation techniques. Moreover, VLP purification represents a substantial portion of the overall production cost, highlighting the urgent need for efficient and scalable downstream processing methods to overcome the current challenges in VLP production. Considering their differing structures and properties, this review systematically summarizes the published results of scalable downstream processes for both enveloped and non-enveloped VLPs. Its aim is to provide a comprehensive overview and significantly contribute to developing future VLP production for pharmaceutical applications, thereby guiding and inspiring further research in this field.
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Affiliation(s)
- Enoch Y Park
- Laboratory of Biotechnology, Faculty of Agriculture, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan; Department of Bioscience, Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan.
| | - Robert Minkner
- Department of Bioscience, Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan.
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3
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Sieg J, Fazel A, Quabius ES, Dempfle A, Wiegand S, Hoffmann M. Therapeutic Impact of Gardasil ® in Recurrent Respiratory Papillomatosis: A Retrospective Study on RRP Patients. Viruses 2025; 17:321. [PMID: 40143250 PMCID: PMC11945329 DOI: 10.3390/v17030321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 02/21/2025] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
Background: Recurrent respiratory papillomatosis (RRP) is a rare, non-malignant disease caused by human papillomavirus (HPV) types 6 and 11. The condition primarily affects the larynx, potentially leading to life-threatening airway obstruction. It is more aggressive in younger patients, necessitating frequent surgical interventions. This study investigates the therapeutic potential of the prophylactic HPV vaccine Gardasil® in RRP patients, focusing on its impact on lesion size and the frequency of surgical interventions. Furthermore, a literature review was conducted to analyze the factors influencing the decision to vaccinate. Methods: A retrospective analysis was conducted on 63 RRP patients treated from 2008 to 2021. Disease burden was assessed using the Derkay score and the annual frequency of laser-surgical ablations. Comparisons were made between pre- and post-vaccination periods in vaccinated patients (n = 18), and between first and second halves of the disease's course in unvaccinated patients (n = 14). Results: A reduction in the frequency of surgical interventions post-vaccination (p < 0.05) could be seen. The cumulated Derkay score per year decreased after second and third vaccination (p < 0.05). The decision to be vaccinated is influenced by multiple factors (e.g., potential side-effects, sociocultural factors, impact of social media, pre-existing conditions and the wider context of the recent pandemic). Conclusions: Gardasil® appears to reduce the frequency of surgery and lessen disease severity in RRP patients, supporting the potential role of HPV vaccination as a therapeutic option for RRP. Moreover, it is crucial to overcome skepticism towards vaccinations to prevent the development of HPV-associated diseases in the first place.
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Affiliation(s)
- Jennifer Sieg
- Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, 24105 Kiel, Germany; (J.S.); (A.F.); (E.S.Q.); (S.W.)
| | - Asita Fazel
- Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, 24105 Kiel, Germany; (J.S.); (A.F.); (E.S.Q.); (S.W.)
| | - Elgar Susanne Quabius
- Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, 24105 Kiel, Germany; (J.S.); (A.F.); (E.S.Q.); (S.W.)
| | - Astrid Dempfle
- Institute of Medical Informatics and Statistics, Christian-Albrechts University Kiel, 24105 Kiel, Germany;
| | - Susanne Wiegand
- Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, 24105 Kiel, Germany; (J.S.); (A.F.); (E.S.Q.); (S.W.)
| | - Markus Hoffmann
- Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, 24105 Kiel, Germany; (J.S.); (A.F.); (E.S.Q.); (S.W.)
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4
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Mosmann TR, McMichael AJ, LeVert A, McCauley JW, Almond JW. Opportunities and challenges for T cell-based influenza vaccines. Nat Rev Immunol 2024; 24:736-752. [PMID: 38698082 DOI: 10.1038/s41577-024-01030-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/27/2024] [Indexed: 05/05/2024]
Abstract
Vaccination remains our main defence against influenza, which causes substantial annual mortality and poses a serious pandemic threat. Influenza virus evades immunity by rapidly changing its surface antigens but, even when the vaccine is well matched to the current circulating virus strains, influenza vaccines are not as effective as many other vaccines. Influenza vaccine development has traditionally focused on the induction of protective antibodies, but there is mounting evidence that T cell responses are also protective against influenza. Thus, future vaccines designed to promote both broad T cell effector functions and antibodies may provide enhanced protection. As we discuss, such vaccines present several challenges that require new strategic and economic considerations. Vaccine-induced T cells relevant to protection may reside in the lungs or lymphoid tissues, requiring more invasive assays to assess the immunogenicity of vaccine candidates. T cell functions may contain and resolve infection rather than completely prevent infection and early illness, requiring vaccine effectiveness to be assessed based on the prevention of severe disease and death rather than symptomatic infection. It can be complex and costly to measure T cell responses and infrequent clinical outcomes, and thus innovations in clinical trial design are needed for economic reasons. Nevertheless, the goal of more effective influenza vaccines justifies renewed and intensive efforts.
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Affiliation(s)
- Tim R Mosmann
- David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
| | - Andrew J McMichael
- Centre for Immuno-Oncology, Old Road Campus Research Building, University of Oxford, Oxford, UK
| | | | | | - Jeffrey W Almond
- The Sir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford, UK
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5
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Berenson AB, Panicker G, Unger ER, Rupp RE, Kuo YF. Immunogenicity of 2 or 3 Doses of 9vHPV Vaccine in U.S. Female Individuals 15 to 26 Years of Age. NEJM EVIDENCE 2024; 3:EVIDoa2300194. [PMID: 38320488 PMCID: PMC11771182 DOI: 10.1056/evidoa2300194] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
BACKGROUND: Within the United States, a 9-valent human papillomavirus (9vHPV) vaccine (HPV-6/11/16/18/31/33/45/52/58) is recommended as a two-dose series among individuals 9 to 14 years of age and a three-dose series among those 15 to 26 years of age. Data comparing two versus three doses of 9vHPV vaccine among individuals 15 to 26 years of age are limited. METHODS: We report on an ongoing, single-blinded, randomized noninferiority trial of the 9vHPV vaccine among individuals 15 to 26 years of age in the United States. Participants were randomly assigned to a two-dose (0 and 6 months) or three-dose (0, 2, and 6 months) schedule. Blood draws to assess antibody titers were planned before the first vaccination and at 1 and 6 months after the final vaccination. The primary outcome was the rate of seroconversion at 1 month after final vaccination. The secondary outcome was the two-dose versus three-dose ratio of antibody geometric mean titers (GMTs) for each of the 9vHPV genotypes at 1 and 6 months after final vaccination. This interim analysis reports results of female participants at 1 month after final vaccination. RESULTS: Of 860 participants screened, 438 were enrolled and randomly assigned to the two-dose (n=217) or three-dose (n=221) group. At 1 month after the final vaccine dose, the seroconversion rate for each of the nine HPV genotypes in the vaccine was 100% among participants in the two-dose group and 99% in the three-dose group. The point estimates of the two-dose versus three-dose ratios of antibody GMTs for eight of the nine HPV genotypes were above unity; the ratio for HPV-45 was 0.86 (95% confidence interval [CI], 0.66 to 1.13). This was also the smallest value for the lower bound of the 95% CI for all nine ratios (ratios above 1 favor the two-dose schedule). No serious adverse events were observed. CONCLUSIONS: In this unplanned interim analysis of U.S. female participants 15 to 26 years of age, two doses of 9vHPV vaccine appear to elicit responses similar to three doses at 1 month postvaccination. We await final results at 6 months following the last vaccine dose. (ClinicalTrials.gov number, NCT03943875.)
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Affiliation(s)
- Abbey B Berenson
- Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX
- Center for Interdisciplinary Research in Women's Health, The University of Texas Medical Branch, Galveston, TX
| | - Gitika Panicker
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases at the Centers for Disease Control and Prevention, Atlanta
| | - Elizabeth R Unger
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases at the Centers for Disease Control and Prevention, Atlanta
| | - Richard E Rupp
- Center for Interdisciplinary Research in Women's Health, The University of Texas Medical Branch, Galveston, TX
- Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX
| | - Yong-Fang Kuo
- Center for Interdisciplinary Research in Women's Health, The University of Texas Medical Branch, Galveston, TX
- Department of Biostatistics & Data Science, The University of Texas Medical Branch, Galveston, TX
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6
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Barbateskovic M, Klingenberg SL, Krauss SR, Kong D, Wu Z, Petersen SB, Kenfelt M, Gluud C. Concentrations, Number of Doses, and Formulations of Aluminium Adjuvants in Vaccines: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials. Vaccines (Basel) 2023; 11:1763. [PMID: 38140168 PMCID: PMC10871092 DOI: 10.3390/vaccines11121763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 11/13/2023] [Accepted: 11/21/2023] [Indexed: 12/24/2023] Open
Abstract
Aluminium adjuvants are commonly used in vaccines to boost the effects of vaccination. Here, we assessed the benefits and harms of different aluminium adjuvants vs. other aluminium adjuvants or vs. the same aluminium adjuvant at other concentrations, administered a different number of doses, or at different particle sizes used in vaccines or vaccine excipients. We conducted a systematic review with meta-analysis and Trial Sequential Analysis to assess the certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). We obtained data from major medical databases until 20 January 2023 and included 10 randomized clinical trials of healthy volunteers. The comparisons assessed higher vs. lower aluminium adjuvant concentrations; higher vs. lower number of doses of aluminium adjuvant; and aluminium phosphate adjuvant vs. aluminium hydroxide adjuvant. For all three comparisons, meta-analyses showed no evidence of a difference on all-cause mortality, serious adverse events, and adverse events considered non-serious. The certainty of evidence was low to very low. None of the included trials reported on quality of life or proportion of participants who developed the disease being vaccinated against. The benefits and harms of different types of aluminium adjuvants, different aluminium concentrations, different number of doses, or different particle sizes, therefore, remain uncertain.
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Affiliation(s)
- Marija Barbateskovic
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.L.K.)
| | - Sarah Louise Klingenberg
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.L.K.)
| | - Sara Russo Krauss
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.L.K.)
| | - Dezhao Kong
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.L.K.)
- The Evidence-Based Medicine Research Center of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China
- Department of Evidence-Based Chinese Medicine Research Centre, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China
| | - Zhangtong Wu
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.L.K.)
- The Evidence-Based Medicine Research Center of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China
- Department of Evidence-Based Chinese Medicine Research Centre, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China
| | - Sesilje B. Petersen
- Department of Occupational and Environmental Medicine, Copenhagen University Hospital—Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark
| | | | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark (S.L.K.)
- Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, 5230 Odense, Denmark
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Tortellini E, Fosso Ngangue YC, Dominelli F, Guardiani M, Falvino C, Mengoni F, Carraro A, Marocco R, Pasculli P, Mastroianni CM, Ciardi MR, Lichtner M, Zingaropoli MA. Immunogenicity and Efficacy of Vaccination in People Living with Human Immunodeficiency Virus. Viruses 2023; 15:1844. [PMID: 37766251 PMCID: PMC10534440 DOI: 10.3390/v15091844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/17/2023] [Accepted: 08/21/2023] [Indexed: 09/29/2023] Open
Abstract
People living with HIV (PLWH) remain at high risk of mortality and morbidity from vaccine-preventable diseases, even though antiretroviral therapy (ART) has restored life expectancy and general well-being. When, which, and how many doses of vaccine should be administered over the lifetime of PLWH are questions that have become clinically relevant. Immune responses to most vaccines are known to be impaired in PLWH. Effective control of viremia with ART and restored CD4+ T-cell count are correlated with an improvement in responsiveness to routine vaccines. However, the presence of immune alterations, comorbidities and co-infections may alter it. In this article, we provide a comprehensive review of the literature on immune responses to different vaccines in the setting of HIV infection, emphasizing the potential effect of HIV-related factors and presence of comorbidities in modulating such responses. A better understanding of these issues will help guide vaccination and prevention strategies for PLWH.
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Affiliation(s)
- Eeva Tortellini
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Yann Collins Fosso Ngangue
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Federica Dominelli
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Mariasilvia Guardiani
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Carmen Falvino
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Fabio Mengoni
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Anna Carraro
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Raffaella Marocco
- Infectious Diseases Unit, SM Goretti Hospital, Sapienza University of Rome, 00185 Latina, Italy; (R.M.); (M.L.)
| | - Patrizia Pasculli
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Claudio Maria Mastroianni
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Maria Rosa Ciardi
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
| | - Miriam Lichtner
- Infectious Diseases Unit, SM Goretti Hospital, Sapienza University of Rome, 00185 Latina, Italy; (R.M.); (M.L.)
- Department of Neurosciences, Mental Health, and Sense Organs, NESMOS, Sapienza University of Rome, 00185 Rome, Italy
| | - Maria Antonella Zingaropoli
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy; (Y.C.F.N.); (F.D.); (M.G.); (C.F.); (F.M.); (A.C.); (P.P.); (C.M.M.); (M.R.C.); (M.A.Z.)
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8
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Morais S, Wissing MD, Khosrow-Khavar F, Burchell AN, Tellier PP, Coutlée F, Waterboer T, El-Zein M, Franco EL. Serologic Response to Human Papillomavirus Genotypes Among Unvaccinated Women: Findings From the HITCH Cohort Study. J Infect Dis 2023; 227:1173-1184. [PMID: 36322543 PMCID: PMC10175069 DOI: 10.1093/infdis/jiac437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/25/2022] [Accepted: 10/31/2022] [Indexed: 11/07/2022] Open
Abstract
BACKGROUND Humoral immune responses may be critical for preventing, controlling, and/or eliminating human papillomavirus (HPV) infection. We analyzed humoral response to natural HPV infection considering phylogenetic relatedness among unvaccinated women. METHODS We included 399 young women attending university/college in Montreal, Canada who were participants of the HITCH cohort. Participants provided blood samples at baseline and 5 follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S-transferase (GST) fusion proteins, and virus-like particles (VLP-L1) of Alphapapillomavirus types were measured using multiplex serology. We assessed correlations and associations between HPV types at baseline using Pearson correlation coefficients (r) and univariable linear regressions. RESULTS At baseline, > 40% were seropositive for GST-L1 antibodies of at least 1 HPV type. Strong correlations between GST-L1 were observed for α9 HPV types: 58-52 (r = 0.86), 58-33 (r = 0.75), 33-52 (r = 0.72), and between GST-E6: 52-11 (r = 0.84), 52-18 (r = 0.79), 58-33 (r = 0.78), 35-11 (r = 0.76). HPV16 VLP-L1 moderately explained variability in HPV16 GST-L1 (regression coefficient [b] = 0.38, R2 = 43.1%), and HPV45 GST-L1 in HPV18 GST-L1 (b = 0.68, R2 = 42.8%). GST-E6 antibodies accounted for a low to moderate proportion of variability in HPV16 and HPV18 GST-E6 (R2 = 6.4%-62.2%). CONCLUSIONS Associations between naturally induced HPV-specific antibodies depend on phylogenetic relatedness.
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Affiliation(s)
- Samantha Morais
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
| | - Michel D Wissing
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
| | | | - Ann N Burchell
- Department of Family and Community Medicine and MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada
| | | | - François Coutlée
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
- Laboratoire de Virologie Moléculaire, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, et Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada
| | - Tim Waterboer
- Infections and Cancer Epidemiology Division, German Cancer Research Center, Heidelberg, Germany
| | - Mariam El-Zein
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
| | - Eduardo L Franco
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
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9
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Tao J, Kapadia J, Fenn N, Almonte AA, Toma E, Murphy M, Nunn A, Su LJ, Chan PA. Human papillomavirus vaccination coverage among sexually active young adults aged 18 to 26 at a sexually transmitted infections clinic. Int J STD AIDS 2023; 34:315-321. [PMID: 36655673 PMCID: PMC10073331 DOI: 10.1177/09564624221146605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND Human papillomavirus (HPV) vaccination is the most effective biomedical intervention for HPV infections. HPV vaccination rate among sexually active young adults is largely unknown. METHODS Patients aged 18-26 years, who attended the Rhode Island Sexually Transmitted Infections Clinic between 2013-2018, were included in the study. We extracted demographics, behavioral characteristics, and HPV vaccination status from electronic medical records. Exploratory logistic regressions were conducted to identify factors associated with vaccination status. RESULTS Among 2729 eligible individuals, the median age was 23 years (interquartile range: 22-25). Only 8.1% of males and 24.8% of females received at least one dose of HPV vaccine. Females were 144% (crude odds ratio [cOR]: 2.44, 95% confidence interval [CI]: 2.03, 2.94) more likely to receive at least one dose of HPV vaccine than males. Being Black/African American (B/AA) or Hispanic/Latino (H/L) was associated with a 21% (cOR: 0.79, 95% CI: 0.62, 1.00) and 34% (cOR: 0.66, 95% CI: 0.53, 0.81) decrease in the odds of vaccination, respectively. CONCLUSIONS HPV vaccination rate was low among sexually active young adults. Gender and racial/ethnic disparities existed in HPV vaccination. Interventions are needed to promote HPV vaccination among sexually active young adults, especially B/AA and H/L communities.
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Affiliation(s)
- Jun Tao
- Department of Medicine, Brown University, Providence, RI, USA
| | - Jhanavi Kapadia
- Department of Medicine, Brown University, Providence, RI, USA
| | - Natalie Fenn
- Department of Medicine, Brown University, Providence, RI, USA
| | - Alexi A Almonte
- Department of Medicine, Brown University, Providence, RI, USA
| | - Emily Toma
- Department of Medicine, Brown University, Providence, RI, USA
| | - Matthew Murphy
- Department of Medicine, Brown University, Providence, RI, USA
| | - Amy Nunn
- Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, RI, USA
| | - L Joseph Su
- School of Public Health, UT Southwestern Medical Center, Dallas, TX, USA
| | - Philip A Chan
- Department of Medicine, Brown University, Providence, RI, USA
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Kitano T, Schwartz KL, Abdulnoor M, Garfield H, Booran NK, Avitzur Y, Teoh CW, Hébert D, Allen U. Immunogenicity of a quadrivalent human papillomavirus vaccine in pediatric kidney and liver transplant recipients. Pediatr Transplant 2023; 27:e14476. [PMID: 36740761 DOI: 10.1111/petr.14476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 12/22/2022] [Accepted: 01/11/2023] [Indexed: 02/07/2023]
Abstract
BACKGROUND Solid-organ transplant recipients are at increased risk of developing human papillomavirus-related diseases. METHODS To evaluate the immunogenicity of a quadrivalent vaccine, a prospective observational study included females aged 12-19 years who had received kidney or liver transplants, or were otherwise healthy volunteers. With the three-dose vaccination, serum antibodies were measured. RESULTS The study included 17 transplant recipients (seven kidney and 10 liver) and 16 healthy participants. Six of seven kidney transplant recipients were on three immunosuppressive medications, whereas 9 of the 10 liver transplant recipients were on one. For the serology within 6 months from the last vaccine dose, the geometric mean titers of human papillomavirus types 6, 11, 16, and 18 were 26.7, 8.6, 35.7, and 42.4 (kidney transplant); 579.2, 569.3, 3097.3, and 835.7 (liver transplant); and 860.5, 638.8, 4391.6, and 902.6 milli-Merck Units/ml (healthy). The seropositivity rates of kidney transplant recipients for the four serotypes ranged from 50% to 75%, while all liver transplant recipients and healthy participants had 100% seropositivity rates for all four types. While there were no statistical differences of titers between liver transplant recipients and healthy participants, the titers of kidney transplant recipients were lower than those of healthy participants for type 6 (p = .034), type 11 (p = .032), and type 16 (p = .032). CONCLUSIONS The results support the recommendation of human papillomavirus vaccination in pediatric transplant recipients given the significant risk of human papillomavirus-related diseases in this population, though immunogenicity was lower in kidney transplant recipients on multiple immunosuppressive medications.
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Affiliation(s)
- Taito Kitano
- Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Kevin L Schwartz
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,Unity Health Toronto, St. Joseph Health Centre, Toronto, Ontario, Canada
| | - Mariana Abdulnoor
- Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Hartley Garfield
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Nasser Khodai Booran
- Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Yaron Avitzur
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Chia Wei Teoh
- Division of Nephrology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Diane Hébert
- Division of Nephrology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Upton Allen
- Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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11
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King LM, Lewnard JA, Niccolai LM. Clinical and Public Health Considerations for HPV Vaccination in Midadulthood: A Narrative Review. Open Forum Infect Dis 2023; 10:ofad004. [PMID: 36726535 PMCID: PMC9887268 DOI: 10.1093/ofid/ofad004] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 01/10/2022] [Indexed: 01/13/2023] Open
Abstract
Human papillomavirus (HPV) is an important cause of anogenital and oropharyngeal cancers, anogenital warts, and recurrent respiratory papillomatosis. Beginning in 2019, US guidelines recommended shared clinical decision-making (SCDM) for HPV vaccination among midadults (27-45 years). We conducted a narrative review of existing literature on HPV vaccination in midadults. The available evidence demonstrates that HPV vaccination in midadults is safe, efficacious, and likely to benefit both HPV-naïve midadults and those with previous infections. However, gaps in knowledge related to HPV vaccination have been identified among clinicians and midadult patients. Universal midadult HPV vaccination in the United States could avert 20 934-37 856 cancer cases over 100 years, costing $141 000-$1 471 000 per quality-adjusted life-year gained. Wide variation in these estimates reflects uncertainties in sexual behavior, HPV natural history, and naturally acquired immunity. Greater awareness among clinicians and midadult patients and broad implementation of SCDM may accelerate progress toward eliminating HPV-associated cancers and other diseases.
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Affiliation(s)
- Laura M King
- Correspondence: Laura M. King, MPH, 2121 Berkeley Way, Berkeley, CA 94704 (); or Joseph A. Lewnard, PhD, 2121 Berkeley Way, Berkeley, CA 94704 ()
| | - Joseph A Lewnard
- Correspondence: Laura M. King, MPH, 2121 Berkeley Way, Berkeley, CA 94704 (); or Joseph A. Lewnard, PhD, 2121 Berkeley Way, Berkeley, CA 94704 ()
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12
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[Recurrent laryngeal papillomatosis]. HNO 2023; 71:77-82. [PMID: 36477391 PMCID: PMC9895037 DOI: 10.1007/s00106-022-01250-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2022] [Indexed: 12/12/2022]
Abstract
Human papillomaviruses (HPV) 6 and 11 cause 90% of recurrent laryngeal papillomatosis (RLP). It is unclear whether recurrences are caused by new infections or the spread of infected cells. Symptomatic and sometimes curative treatment is laser surgery or conventional microsurgical removal. RLP surgery aims to relieve shortness of breath and improve the voice. Patients (especially children) are affected by voice problems, repetitive surgeries, pulmonary manifestations, and psychological trauma. Vaccination with Gardasil 9 (Merck & Co., Rahway, NJ, USA) prevents new infections with HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 and induces vaccine antigen-specific antibodies and CD4+ T helper cells. According to current studies, RLP can be avoided with prophylactic vaccination. The treatment is associated with a general vaccination risk (European Medicines Agency approval: girls and boys from 9 years). Studies also show that the vaccine after removal of HPV-associated neoplasia/papilloma prevents recurrences. Extension of the vaccination recommendation to prevent recurrences of HPV-associated diseases in men may promote applicability and herd immunity. For rare and treatment-refractory cases with laryngotracheal involvement, systemic therapy with bevacizumab (e.g. Avastin; Genentech, San Francisco, CA, USA), a VEGF antibody, is a promising adjuvant treatment option.
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13
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Martins SA, Santos J, Silva RDM, Rosa C, Cabo Verde S, Correia JDG, Melo R. How promising are HIV-1-based virus-like particles for medical applications. Front Cell Infect Microbiol 2022; 12:997875. [PMID: 36275021 PMCID: PMC9585283 DOI: 10.3389/fcimb.2022.997875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 09/23/2022] [Indexed: 11/26/2022] Open
Abstract
New approaches aimed at identifying patient-specific drug targets and addressing unmet clinical needs in the framework of precision medicine are a strong motivation for researchers worldwide. As scientists learn more about proteins that drive known diseases, they are better able to design promising therapeutic approaches to target those proteins. The field of nanotechnology has been extensively explored in the past years, and nanoparticles (NPs) have emerged as promising systems for target-specific delivery of drugs. Virus-like particles (VLPs) arise as auspicious NPs due to their intrinsic properties. The lack of viral genetic material and the inability to replicate, together with tropism conservation and antigenicity characteristic of the native virus prompted extensive interest in their use as vaccines or as delivery systems for therapeutic and/or imaging agents. Owing to its simplicity and non-complex structure, one of the viruses currently under study for the construction of VLPs is the human immunodeficiency virus type 1 (HIV-1). Typically, HIV-1-based VLPs are used for antibody discovery, vaccines, diagnostic reagent development and protein-based assays. This review will be centered on the use of HIV-1-based VLPs and their potential biomedical applications.
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Affiliation(s)
- Sofia A. Martins
- Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
| | - Joana Santos
- Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
| | - Rúben D. M. Silva
- Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
| | - Cátia Rosa
- Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
| | - Sandra Cabo Verde
- Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
- Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
| | - João D. G. Correia
- Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
- Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
| | - Rita Melo
- Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
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Mukhopadhyay E, Brod F, Angell‐Manning P, Green N, Tarrant RD, Detmers FJ, Bolam EJ, Baleanu IN, Hobson M, Whale G, Morris SJ, Ashfield R, Gilbert SC, Jin J, Draper SJ, Moyle SP, Berrie EL, Hill AVS. Production of a high purity, C-tagged hepatitis B surface antigen fusion protein VLP vaccine for malaria expressed in Pichia pastoris under cGMP conditions. Biotechnol Bioeng 2022; 119:2784-2793. [PMID: 35822551 PMCID: PMC9546177 DOI: 10.1002/bit.28181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 06/09/2022] [Accepted: 07/10/2022] [Indexed: 11/21/2022]
Abstract
Virus-like particles (VLPs) induce strong humoral and cellular responses and have formed the basis of some currently licensed vaccines. Here, we present the method used for the production of R21, a VLP-based anti-sporozoite malaria vaccine, under current Clinical Good Manufacturing Practice regulations (cGMP). Previous preclinical studies in BALB/c mice showed that R21 produced almost complete protection against sporozoite challenge with transgenic Plasmodium berghei parasites. Here, we have modified the preclinical production process to enable the production of sufficient quantities of highly pure, clinical-grade material for use in human clinical trials. The R21 construct was re-engineered to include a C-tag to allow affinity-based separation from the major contaminant alcohol oxidase 1 (AOX 1, ~74 kDa). To our knowledge, this is the first use of C-tag technology to purify a VLP vaccine candidate for use in human clinical trials. The R21 vaccine has shown high-level efficacy in an African Phase IIb trial, and multiple clinical trials are underway to assess the safety and efficacy of the vaccine. Our findings support the future use of C-tag platform technologies to enable cGMP-compliant biomanufacturing of high purity yeast-expressed VLP-based vaccines for early phase clinical trials when clinical grade material is required in smaller quantities in a quick time frame.
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Affiliation(s)
- Ekta Mukhopadhyay
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Florian Brod
- The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Philip Angell‐Manning
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Nicola Green
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Richard D. Tarrant
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | | | - Emma J. Bolam
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Ioana N. Baleanu
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Mark Hobson
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Gary Whale
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Susan J. Morris
- The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Rebecca Ashfield
- The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Sarah C. Gilbert
- The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Jing Jin
- The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Simon J. Draper
- The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Sarah P. Moyle
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Eleanor L. Berrie
- Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Adrian V. S. Hill
- The Jenner Institute, Nuffield Department of MedicineUniversity of OxfordOxfordUK
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15
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Prabhu PR, Carter JJ, Galloway DA. B Cell Responses upon Human Papillomavirus (HPV) Infection and Vaccination. Vaccines (Basel) 2022; 10:vaccines10060837. [PMID: 35746445 PMCID: PMC9229470 DOI: 10.3390/vaccines10060837] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/20/2022] [Accepted: 05/23/2022] [Indexed: 02/01/2023] Open
Abstract
Infection with human papillomavirus (HPV) is the necessary cause of cervical cancer. Availability of vaccines against HPV makes it a highly preventable disease. HPV vaccines act through type-specific neutralizing antibodies produced by antigen-specific plasma cells known as long-lived plasma cells (LLPC). However, just as any other vaccine, success of HPV vaccine is attributed to the immunologic memory that it builds, which is largely attained through generation and maintenance of a class of B cells named memory B cells (Bmem). Both LLPCs and Bmems are important in inducing and maintaining immune memory and it is therefore necessary to understand their role after HPV vaccination to better predict outcomes. This review summarizes current knowledge of B-cell responses following HPV vaccination and natural infection, including molecular signatures associated with these responses.
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16
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Barnard-Mayers R, Kouser H, Cohen JA, Tassiopoulos K, Caniglia EC, Moscicki AB, Campos NG, Caunca MR, Seage GRS, Murray EJ. A case study and proposal for publishing directed acyclic graphs: The effectiveness of the quadrivalent human papillomavirus vaccine in perinatally HIV Infected girls. J Clin Epidemiol 2022; 144:127-135. [PMID: 34998951 PMCID: PMC8977269 DOI: 10.1016/j.jclinepi.2021.12.028] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 12/22/2021] [Accepted: 12/29/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Developing a causal graph is an important step in etiologic research planning and can be used to highlight data flaws and irreparable bias and confounding. As a case study, we consider recent findings that suggest human papillomavirus (HPV) vaccine is less effective against HPV-associated disease among girls living with HIV compared to girls without HIV. OBJECTIVES To understand the relationship between HIV status and HPV vaccine effectiveness, it is important to outline the key assumptions of the causal mechanisms before designing a study to investigate the effect of the HPV vaccine in girls living with HIV infection. METHODS We present a causal graph to describe our assumptions and proposed approach to explore this relationship. We hope to obtain feedback on our assumptions before data analysis and exemplify the process for designing causal graphs to inform an etiologic study. CONCLUSION The approach we lay out in this paper may be useful for other researchers who have an interest in using causal graphs to describe and assess assumptions in their own research before undergoing data collection and/or analysis.
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Affiliation(s)
| | - Hiba Kouser
- Department of Epidemiology, Boston University, Boston, MA, USA; Breast Oncology Center, Dana Farber Cancer Institute, Boston, MA, USA
| | - Jamie A Cohen
- Health Policy PhD Program, Harvard University, Cambridge, MA, USA
| | | | - Ellen C Caniglia
- Department of Population Health, NYU School of Medicine, New York, NY, USA
| | - Anna-Barbara Moscicki
- Department of Pediatrics, Division of Adolescent Medicine, University of California, Los Angeles, CA, USA
| | - Nicole G Campos
- Center for Health Decision Science, Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Michelle R Caunca
- Medical Scientist Training Program, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - George R Seage Seage
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
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17
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Yousefi Z, Aria H, Ghaedrahmati F, Bakhtiari T, Azizi M, Bastan R, Hosseini R, Eskandari N. An Update on Human Papilloma Virus Vaccines: History, Types, Protection, and Efficacy. Front Immunol 2022; 12:805695. [PMID: 35154080 PMCID: PMC8828558 DOI: 10.3389/fimmu.2021.805695] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 12/31/2021] [Indexed: 12/18/2022] Open
Abstract
Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. Early prevention with HPV vaccination is a safe and effective method against this disease. HPV vaccines provided more protection against several oncogenic HPV strains. Three prophylactic HPV vaccines have been approved to target high-risk HPV types and protect against HPV-related disorders. These existing vaccines are based on the recombinant DNA technology and purified L1 protein that is assembled to form HPV empty shells. The prophylactic vaccines are highly immunogenic and can induce production of specific neutralizing antibodies. However, therapeutic vaccines are different from these prophylactic vaccines. They induced cell-mediated immunity against transformed cells, instead of neutralizing antibodies. The second generation of prophylactic HPV vaccines, made from alternative viral components using cost-effective production strategies, is undergoing clinical evaluation. The purpose of this review is to provide a complete and up-to-date review of the types of HPV vaccines and the efficiency of each of them for readers.
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Affiliation(s)
- Zahra Yousefi
- School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Hamid Aria
- Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Farhoodeh Ghaedrahmati
- Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Tahereh Bakhtiari
- Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahdieh Azizi
- Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Bastan
- Department of Immunopharmacology, Faculty of Medicine, Karaj University of Medical Sciences, Alborz, Iran
| | - Reza Hosseini
- Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nahid Eskandari
- Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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18
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Kurosawa M, Sekine M, Yamaguchi M, Kudo R, Hanley SJB, Hara M, Adachi S, Ueda Y, Miyagi E, Ikeda S, Yagi A, Enomoto T. Long-Term Effects of Human Papillomavirus Vaccination in Clinical Trials and Real-World Data: A Systematic Review. Vaccines (Basel) 2022; 10:vaccines10020256. [PMID: 35214713 PMCID: PMC8877934 DOI: 10.3390/vaccines10020256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/03/2022] [Accepted: 02/04/2022] [Indexed: 12/04/2022] Open
Abstract
The preventive effect of HPV vaccines against anogenital and oropharyngeal cancers has been proven in both clinical trials and real-world data. We reviewed the published evidence about the long-term efficacy and effectiveness of the HPV vaccine in available papers of clinical trials and real-world data. As far as we searched, the longest period of preventive effect for the bivalent, 4-valent, and 9-valent vaccine were 11 years in the Costa Rica trial, 14 years in the FUTURE II, and 8 years in the LTFU extension study of V503-002 and the Scandinavian study, respectively. The sustained clinical effect during the observation period was longest for the 4-valent vaccine. In real-world data, the longest observation period of the vaccine effectiveness was 12 years in an Australian study for the 4-valent vaccine. On the other hand, the longest period of long-term persistence of HPV vaccine-induced seropositivity was 14 years in FUTURE II for the 4-valent vaccine. For the bivalent vaccine, additional long-term follow-up studies may not have been planned due to the launch of the 4-valent and 9-valent vaccines. In some studies of the 9-valent vaccine, the results have not yet been published because of the short observation period. The additional results are expected in the future. In a national immunization program, most girls and boys are inoculated with HPV vaccine by the time puberty begins; thus, it is important to monitor the vaccine effect at least until the sexually active period in their 20s and 30s.
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Affiliation(s)
- Megumi Kurosawa
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
| | - Masayuki Sekine
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
- Correspondence:
| | - Manako Yamaguchi
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
| | - Risa Kudo
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
| | - Sharon J. B. Hanley
- Center for Environmental and Health Sciences, Hokkaido University, Sapporo 060-8638, Japan;
| | - Megumi Hara
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan;
| | - Sosuke Adachi
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
| | - Yutaka Ueda
- Departments of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; (Y.U.); (A.Y.)
| | - Etsuko Miyagi
- Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan;
| | - Sayaka Ikeda
- Division of Surveillance and Policy Evaluation, Institute for Cancer Control, National Cancer Center, Tokyo 104-0045, Japan;
| | - Asami Yagi
- Departments of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; (Y.U.); (A.Y.)
| | - Takayuki Enomoto
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
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Zhang C, Kou Z, Li R, Ji F, Lin X, Xu A, Song Y, Tao Z. Genomic diversity of human papillomavirus type 6 from patients with condyloma acuminatum in Eastern China. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2021; 96:105146. [PMID: 34800713 DOI: 10.1016/j.meegid.2021.105146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 11/12/2021] [Accepted: 11/15/2021] [Indexed: 06/13/2023]
Abstract
OBJECTIVE Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts both men and women. However, there is limited data on its genomic characterization in mainland China. The aim of this study was to understand the complete genomic diversity of HPV6 from patients with condyloma acuminatum (CA) and to explore the prevalence of different variant lineages/sublineages in eastern China. METHODS CA samples were collected in 3 hospitals in Shandong Province, China from January 2020 to March 2021. DNA extraction, PCR amplification, Sanger sequencing and sequence assembly were performed on HPV6-positive samples. The complete genomes obtained in this study were analyzed phylogenetically with global HPV6 sequences in GenBank database using MEGA 11. RESULTS A total of 55 complete genomic sequences of HPV6 were obtained in this study. They were classified as HPV6 variant lineage A (n = 20), sublineage B1 (n = 34) and sublineage B3 (n = 1) by phylogenetic analysis. Sequence alignment showed E1, E5A, E5B, L1, L2, LCR were relatively highly variable regions for sublineage B1 whereas E1, E5A, L2 for lineage A. Both phylogenetic trees of lineage A and sublineage B1 composed of two main branches. Chinese sequences of lineage A segregated into the major branch while those in sublineage B1 belonged to both branches. Genomic divergence between sequences from China and other countries was 0.00% - 0.33% in lineage A and 0.00% - 0.40% in sublineage B1. CONCLUSIONS This is the first study on HPV variant lineages circulating in mainland China. The results revealed that lineage A and sublineage B1 were prevalent and they had different highly variable regions. Further surveillance is needed to understand the dynamic change of different variants in the population.
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Affiliation(s)
- Cui Zhang
- Department of Microbiology, School of Public Health, Cheeloo College of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, PR China
| | - Zengqiang Kou
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, PR China
| | - Renpeng Li
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, PR China
| | - Feng Ji
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, PR China
| | - Xiaojuan Lin
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, PR China
| | - Aiqiang Xu
- Department of Microbiology, School of Public Health, Cheeloo College of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, PR China; Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, PR China
| | - Yanyan Song
- Department of Microbiology, School of Public Health, Cheeloo College of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, PR China.
| | - Zexin Tao
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, PR China.
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Huang R, Gan R, Zhang D, Xiao J. The comparative safety of human papillomavirus vaccines: A Bayesian network meta-analysis. J Med Virol 2021; 94:729-736. [PMID: 34453758 DOI: 10.1002/jmv.27304] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 08/26/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS The safety of human papillomavirus (HPV) vaccines, one of the major challenges to public vaccination, has been controversial. This study assessed the adverse reactions of various HPV vaccines, including bivalent HPV (2vHPV), quadrivalent HPV (4vHPV), and 9-valent HPV (9vHPV) vaccines. METHODS PubMed, Embase, and Central databases were searched for randomized controlled trials (RCTs) on the comparative safety of HPV vaccines. A network meta-analysis was performed based on the Bayesian framework random-effects model. RESULTS This study included 23 RCTs. Analysis across these reports indicated that the 2vHPV vaccine was associated with significantly more systemic adverse events than the 4vHPV vaccine (risk ratio [RR]: 1.28, 95% credible interval [CrI]: 1.14-1.44), 9vHPV vaccine (RR: 1.25, 95% CrI: 1.06-1.49), and placebo (RR: 1.31, 95% CrI: 1.18-1.46). However, there were no statistically significant differences in serious adverse events between the vaccinated and placebo groups. For injection-site adverse events, there were substantial inconsistencies between the direct and indirect effects; therefore, the analysis results of the safety were presented only for systemic and serious adverse events. CONCLUSIONS The 2vHPV vaccine resulted in more systemic adverse events than other vaccines and placebo. No significant differences in serious adverse events were observed. Further studies are needed to obtain more information regarding the safety of HPV vaccines.
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Affiliation(s)
- Rongdong Huang
- Center for Vaccine Clinical Research, Fujian Provincial Center for Disease Control and Prevention, Fuzhou, China
| | - Ruihuan Gan
- Department of Preventive Dentistry, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, China
| | - Dongjuan Zhang
- Center for Vaccine Clinical Research, Fujian Provincial Center for Disease Control and Prevention, Fuzhou, China
| | - Jianxiong Xiao
- Center for Vaccine Clinical Research, Fujian Provincial Center for Disease Control and Prevention, Fuzhou, China
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21
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Sabeena S, Ravishankar N. Postvaccination prevalence of vaccine-Human Papillomavirus (vHPV) genotypes among the target population: A systematic review and meta-analysis. J Med Virol 2021; 93:4659-4667. [PMID: 33764530 DOI: 10.1002/jmv.26968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 03/15/2021] [Accepted: 03/22/2021] [Indexed: 11/07/2022]
Abstract
Human Papillomavirus (HPV) vaccines are safe and are highly effective in reducing the prevalence of HPV infections and subsequent HPV associated diseases in the target population. A systematic review and meta-analysis was carried out searching electronic databases for articles published between January 2007 and September 2020 reporting the prevalence estimates of vaccine HPV (vHPV) types in women who had received one or more doses of quadrivalent or bivalent vaccines. This systematic review was based on standard systematic review guidelines and the meta-analysis was performed by pooling the HPV vaccine type prevalence data with 95% confidence interval (CI) among 16,929 young women who had received the prophylactic HPV vaccines before the age of 27 years. The overall pooled prevalence of vHPV types was.0.04 (95% CI: 0.02, 0.05). The meta-analysis concludes that prophylactic HPV vaccination before the age of 27 years results in a decline of vHPV types in young women.
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Affiliation(s)
- Sasidharanpillai Sabeena
- Manipal Institute of Virology, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India
| | - Nagaraja Ravishankar
- Department of Biostatistics, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
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Huber B, Wang JW, Roden RBS, Kirnbauer R. RG1-VLP and Other L2-Based, Broad-Spectrum HPV Vaccine Candidates. J Clin Med 2021; 10:1044. [PMID: 33802456 PMCID: PMC7959455 DOI: 10.3390/jcm10051044] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 02/24/2021] [Accepted: 02/26/2021] [Indexed: 12/19/2022] Open
Abstract
Licensed human papillomavirus (HPV) vaccines contain virus-like particles (VLPs) self-assembled from L1 major-capsid proteins that are remarkably effective prophylactic immunogens. However, the induced type-restricted immune response limits coverage to the included vaccine types, and costly multiplex formulations, restrictive storage and distribution conditions drive the need for next generation HPV vaccines. Vaccine candidates based upon the minor structural protein L2 are particularly promising because conserved N-terminal epitopes induce broadly cross-type neutralizing and protective antibodies. Several strategies to increase the immunological potency of such epitopes are being investigated, including concatemeric multimers, fusion to toll-like receptors ligands or T cell epitopes, as well as immunodominant presentation by different nanoparticle or VLP structures. Several promising L2-based vaccine candidates have reached or will soon enter first-in-man clinical studies. RG1-VLP present the HPV16L2 amino-acid 17-36 conserved neutralization epitope "RG1" repetitively and closely spaced on an immunodominant surface loop of HPV16 L1-VLP and small animal immunizations provide cross-protection against challenge with all medically-significant high-risk and several low-risk HPV types. With a successful current good manufacturing practice (cGMP) campaign and this promising breadth of activity, even encompassing cross-neutralization of several cutaneous HPV types, RG1-VLP are ready for a first-in-human clinical study. This review aims to provide a general overview of these candidates with a special focus on the RG1-VLP vaccine and its road to the clinic.
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Affiliation(s)
- Bettina Huber
- Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria;
| | - Joshua Weiyuan Wang
- Department of Pathology, The Johns Hopkins University, Baltimore, MD 21218, USA; (J.W.W.); (R.B.S.R.)
- PathoVax LLC, Baltimore, MD 21205, USA
| | - Richard B. S. Roden
- Department of Pathology, The Johns Hopkins University, Baltimore, MD 21218, USA; (J.W.W.); (R.B.S.R.)
- Department of Gynecology and Obstetrics, The Johns Hopkins University, Baltimore, MD 21218, USA
- Department of Oncology, The Johns Hopkins University, Baltimore, MD 21218, USA
| | - Reinhard Kirnbauer
- Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria;
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Tan HX, Juno JA, Lee WS, Barber-Axthelm I, Kelly HG, Wragg KM, Esterbauer R, Amarasena T, Mordant FL, Subbarao K, Kent SJ, Wheatley AK. Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques. Nat Commun 2021; 12:1403. [PMID: 33658497 PMCID: PMC7930087 DOI: 10.1038/s41467-021-21665-8] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 02/04/2021] [Indexed: 12/23/2022] Open
Abstract
SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.
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Affiliation(s)
- Hyon-Xhi Tan
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Jennifer A Juno
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Wen Shi Lee
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Isaac Barber-Axthelm
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Hannah G Kelly
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
- Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC, Australia
| | - Kathleen M Wragg
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Robyn Esterbauer
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
- WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Thakshila Amarasena
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Francesca L Mordant
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Kanta Subbarao
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
- WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Stephen J Kent
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
- Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC, Australia.
- Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia.
| | - Adam K Wheatley
- Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
- Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC, Australia.
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Cross-neutralizing antibody titres against non-vaccine types induced by a recombinant trivalent HPV vaccine (16/18/58) in rhesus macaques. PAPILLOMAVIRUS RESEARCH 2020; 10:100209. [PMID: 33197649 PMCID: PMC7704424 DOI: 10.1016/j.pvr.2020.100209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 11/05/2020] [Accepted: 11/06/2020] [Indexed: 12/05/2022]
Abstract
Human papillomavirus (HPV) causes not only most cervical cancers but also cancers of the vagina, vulva, penis, anus, rectum, and oropharynx. Every year, 200,000 women die of cervical cancer in the world, and China accounts for about 10%. HPV vaccines are effective in preventing HPV infections thus HPV-related cancers worldwide. Studies on the clinical trials of the 2v Cervarix™ and the 4v Gardasil® have suggested that immunization with either of these vaccines provided some level of protection against other HPV types that are closely related to the types contained in the vaccines. Here we conducted a preliminary evaluation on the ability to induce cross-neutralizing antibodies in rhesus monkeys by a 3v HPV vaccine that targets HPV16, 18, and 58 and it is specifically designed for Chinese women. We found that this vaccine is no less than Gardasil® in terms of the ability to induce NAbs against non-vaccine types of HPV in rhesus macaques. These results provided evidence from the immunogenicity point of view that the KLWS 3v HPV vaccine is a strong competitor to the imported 2v and 4v HPV vaccines currently available on the market.
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Luvero D, Lopez S, Bogani G, Raspagliesi F, Angioli R. From the Infection to the Immunotherapy in Cervical Cancer: Can We Stop the Natural Course of the Disease? Vaccines (Basel) 2020; 8:vaccines8040597. [PMID: 33050484 PMCID: PMC7712259 DOI: 10.3390/vaccines8040597] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 10/05/2020] [Accepted: 10/08/2020] [Indexed: 11/16/2022] Open
Abstract
Cervical cancer (CC) is the second leading cause of cancer death in women aged 20–39 years. Persistent infection with oncogenic types of human papillomavirus (HPV) represents the most important risk factor for the development of cervical cancer. Three HPVs vaccines are currently on the global market: bivalent, quadrivalent, and nonavalent. The nonavalent vaccine provides protection against almost 90% of HPV-related CC. Despite availability of primary and secondary prevention measures, CC persists as one of the most common cancers among women around the world. Although CC is a largely preventable disease, management of persistent or recurrent CC no longer amenable to control with surgery or radiation therapy has not improved significantly with the progress of modern chemotherapy and disseminated carcinoma of the cervix remains a discouraging clinical entity with a 1-year survival rate between 10% and 15%. Over the last few years, there has been increasing interest in immunotherapy as a strategy to fight tumors. This article focuses on recent discoveries about the HPV vaccine and immunotherapies in the prevention and treatment of CC, highlighting the future view.
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Affiliation(s)
- Daniela Luvero
- Department of Gynecology, University Campus Biomedico, 00128 Rome, Italy;
- Correspondence: ; Tel.: +39-333-3222183
| | - Salvatore Lopez
- Department of Gynecologic Oncology, IRCCS National Cancer Institute, 20133 Milan, Italy; (S.L.); (G.B.); (F.R.)
- Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy
| | - Giorgio Bogani
- Department of Gynecologic Oncology, IRCCS National Cancer Institute, 20133 Milan, Italy; (S.L.); (G.B.); (F.R.)
| | - Francesco Raspagliesi
- Department of Gynecologic Oncology, IRCCS National Cancer Institute, 20133 Milan, Italy; (S.L.); (G.B.); (F.R.)
| | - Roberto Angioli
- Department of Gynecology, University Campus Biomedico, 00128 Rome, Italy;
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Moscicki AB, Karalius B, Tassiopoulos K, Yao TJ, Jacobson DL, Patel K, Purswani M, Seage GR. Human Papillomavirus Antibody Levels and Quadrivalent Vaccine Clinical Effectiveness in Perinatally Human Immunodeficiency Virus-infected and Exposed, Uninfected Youth. Clin Infect Dis 2020; 69:1183-1191. [PMID: 30927547 DOI: 10.1093/cid/ciy1040] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Persons who are infected with human immunodeficiency virus (HIV) are at high risk of human papillomavirus (HPV)-associated cancers. The objectives are to compare antibody titers to HPV 6, 11, 16, and 18 and rate of abnormal cytology between perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth. METHODS This is a prospective observational cohort study of HPV4 vaccinated youth performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Seroconversion and geometric mean titer (GMT) against HPV types 6, 11, 16, and 18 were calculated. Vaccine effectiveness included rates of abnormal cervical cytology and genital warts. RESULTS Seroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62% of 310 vaccinated PHIV youth compared to 94%, 96%, 99%, and 87% of 148 vaccinated PHEU youth, respectively (P < .05 for all comparisons). GMTs were lower in the PHIV vs PHEU within each category of HPV4 doses received. Higher GMTs were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination, as well as shorter duration between last vaccine dose and antibody specimen. Abnormal cytology occurred in 33 of 56 PHIV and 1 of 7 PHEU sexually active vaccinated females, yielding incidence rates per 100 person-years of 15.0 (10.9 to 20.6) and 2.9 (0.4 to 22.3), respectively. CONCLUSION Antibody titers to HPV4 were lower for all serotypes in PHIV compared to PHEU youth. Protection against abnormal cytology was also diminished in sexually active PHIV females.
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Affiliation(s)
- Anna-Barbara Moscicki
- Department of Pediatrics, Division of Adolescent Medicine, University of California, Los Angeles
| | - Brad Karalius
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Katherine Tassiopoulos
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Tzy-Jyun Yao
- Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Denise L Jacobson
- Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Kunjal Patel
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Murli Purswani
- Division of Pediatric Infectious Disease, Bronx-Lebanon Hospital Center, Icahn School of Medicine at Mount Sinai, New York
| | - George R Seage
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
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Lai L, Ault K, Rouphael N, Beck A, Domjahn B, Xu Y, Anderson EJ, Cheng A, Nakamura A, Hoagland RJ, Kelley C, Edupuganti S, Mask K, Nesin M, Unger ER, Panicker G, David H, Mulligan MJ. Duration of Cellular and Humoral Responses after Quadrivalent Human Papillomavirus Vaccination in Healthy Female Adults with or without Prior Type 16 and/or 18 Exposure. Vaccines (Basel) 2020; 8:vaccines8030348. [PMID: 32629943 PMCID: PMC7563427 DOI: 10.3390/vaccines8030348] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/22/2020] [Accepted: 06/24/2020] [Indexed: 12/14/2022] Open
Abstract
Human papillomavirus virus (HPV) vaccines aim to provide durable protection and are ideal to study the association of cellular with humoral responses. We assessed the duration and characteristics of immune responses provided by the quadrivalent HPV (4vHPV) vaccine in healthy female adults with or without prior exposure with type 16 and 18 HPV. In a prospective cohort, vaccine naïve females received three doses of 4vHPV vaccine and were followed for two years to assess cellular (intracellular cytokine staining, proliferation and B cell ELISpot assays) and humoral (multiplex L1/L2 viral-like particles (VLP) and M4 ELISAs) responses. Frequencies of vaccine-specific CD4+ T cells correlated with antibody responses. Higher HPV antibody titers were found at all time points in participants previously exposed to HPV, except for anti-HPV-18 at Day 187 (one week post the third vaccination). Retrospective cohorts enrolled females who had previously received two or three 4vHPV doses and tested antibody titers by M4 ELISA and pseudovirion neutralization assay along with memory B cells (MBCs). Almost all women enrolled in a retrospective cohort with two prior doses and all women enrolled in a retrospective cohort with three prior doses had sustained antibody and memory responses. Our findings indicate that HPV vaccination induces a long-lasting, robust cellular and humoral immune responses.
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Affiliation(s)
- Lilin Lai
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
| | - Kevin Ault
- Department of Obstetrics and Gynecology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA;
| | - Nadine Rouphael
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
- Correspondence: ; Tel.: +1-404-712-1435
| | - Allison Beck
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
| | - Briyana Domjahn
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
| | - Yongxian Xu
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
| | - Evan J. Anderson
- Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive NE, Atlanta, GA 30322, USA;
| | - Andrew Cheng
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
| | - Aya Nakamura
- The EMMES Company, LLC, 401 N. Washington St., Suite 700, Rockville, MD 20850, USA;
| | | | - Colleen Kelley
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
| | - Srilatha Edupuganti
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
| | - Karen Mask
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
| | - Mirjana Nesin
- Division of Microbiology and Infectious Diseases, NIAID, NIH, 5601 Fishers Lane, Rockville, MD 20892-9825, USA; (M.N.); (H.D.)
| | - Elizabeth R. Unger
- Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30329, USA; (E.R.U.); (G.P.)
| | - Gitika Panicker
- Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30329, USA; (E.R.U.); (G.P.)
| | - Hagit David
- Division of Microbiology and Infectious Diseases, NIAID, NIH, 5601 Fishers Lane, Rockville, MD 20892-9825, USA; (M.N.); (H.D.)
| | - Mark J. Mulligan
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA; (L.L.); (A.B.); (B.D.); (Y.X.); (A.C.); (C.K.); (S.E.); (K.M.); (M.J.M.)
- New York University Langone Vaccine Center, Alexandria Center for Life Sciences (West Tower), 430 E 29th St, Room 304, New York, NY 10016, USA
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Incidence, Clearance, and Persistence of Anal Human Papillomavirus in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Implications for Human Papillomavirus Vaccination. Sex Transm Dis 2020; 46:229-233. [PMID: 30870323 DOI: 10.1097/olq.0000000000000958] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Men who have sex with men living with human immunodeficiency virus have a high risk of anal cancer. We estimate the likely benefit of human papillomavirus (HPV) vaccination among participants of the Anal Cancer Examination study. METHODS Anal swabs were collected for the detection and genotyping of anal HPV DNA by linear array (Roche Diagnostics) in this 2-year multicenter prospective cohort. We calculated the proportion of men, stratified by age, without detectable vaccine type-specific DNA. RESULTS Overall, 255 men, with a median age of 50 years (interquartile range, 44-56 years) contributed 488.9 person-years of follow-up. After 2 years of follow-up, 149 (58%; 95% confidence interval [CI], 52-65) had at least 1 high-risk HPV (HRHPV), and 71 (28%, 95% CI, 22-34) had HPV types 16/18 detected. Assuming that DNA-negative men would receive vaccine protection, vaccination at baseline could potentially prevent HRHPV infection in 10.2% of men (95% CI, 6.8-14.6, 26 of 255) 2 years later from incident HRHPV covered by the bivalent and quadrivalent vaccine, and 29.4% of men (95% CI, 23.9-35.4, 75/255) from incident HRHPV covered by the nonavalent vaccine. CONCLUSION Though there is high prevalence of anal HPV in men who have sex with men living with human immunodeficiency virus, there was also a high incidence of HRHPV vaccine types in the 2-year follow-up, indicating potential for prevention if these men were not previously infected with HPV vaccine types and were vaccinated at their baseline visit.
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Ballestas SA, Shelly S, Soriano RM, Klein A. Trends in recurrent respiratory papillomatosis treatment. ACTA OTORRINOLARINGOLOGICA ESPANOLA 2020; 72:109-120. [PMID: 32312478 DOI: 10.1016/j.otorri.2019.11.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/23/2019] [Accepted: 11/08/2019] [Indexed: 11/27/2022]
Abstract
Recurrent respiratory papillomatosis (RRP) consist of benign tumours along the airway caused by human papillomavirus infection. Papillomas may cause changes in phonation and obstruct the airway. The purpose of this study was to evaluate the different surgical and adjuvant therapies available for the treatment of this condition reported between 2014-2018. A PubMed search was performed for RRP treatment articles published between 2014 -2018. Forty articles that encompassed 1425 patients with RRP met the criteria. Of these, 24 articles evaluate the use of adjuvant therapies such as bevacizumab, human papillomavirus vaccine and cidofovir. There has been an increase in adjuvant therapy options for RRP in the literature in recent years. An awareness of these options highlights gaps and opportunities in the care of these patients, opens the door to new protocols to control disease and increase intersurgical intervals, and guides us towards new management paradigms in the future.
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Affiliation(s)
- Samir A Ballestas
- Departamento de Otorrinolaringología y Cirugía de Cabeza y Cuello, Emory University School of Medicine, Atlanta, Estados Unidos
| | - Sandeep Shelly
- Departamento de Otorrinolaringología y Cirugía de Cabeza y Cuello, Emory University School of Medicine, Atlanta, Estados Unidos
| | - Roberto M Soriano
- Departamento de Otorrinolaringología y Cirugía de Cabeza y Cuello, Emory University School of Medicine, Atlanta, Estados Unidos
| | - Adam Klein
- Departamento de Otorrinolaringología y Cirugía de Cabeza y Cuello, Emory University School of Medicine, Atlanta, Estados Unidos.
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31
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Mboumba Bouassa RS, Péré H, Jenabian MA, Veyer D, Meye JF, Touzé A, Bélec L. Natural and vaccine-induced B cell-derived systemic and mucosal humoral immunity to human papillomavirus. Expert Rev Anti Infect Ther 2020; 18:579-607. [PMID: 32242472 DOI: 10.1080/14787210.2020.1750950] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Human papillomavirus (HPV) are the causative agent of mucosal neoplasia. Both cervical, anal and oropharyngeal cancers incidence is constantly increasing, making the HPV infection, a significant worldwide concern. Together, the CD8+ T cytotoxic cell-mediated response and the HPV-specific antibody response control most of the HPV infections before the development of cancers.Areas covered: We searched the MEDLINE and EMBASE databases and identified 228 eligible studies from 1987 to 2019 which examines both naturally acquired and vaccine induced humoral immunity against HPV infection in female and male subjects from worldwide origin. Herein, we synthesize current knowledge on the features of systemic and mucosal humoral immunity against HPV. We discuss the issues of the balance between the viral clearance or the escape to the host immune response, the differences between natural and vaccine-induced HPV-specific antibodies and their neutralizing capability. We also discuss the protection afforded after natural infection or following prophylactic vaccination.Expert opinion: Understanding the antibody response induced by HPV infection has led to the design of first-generation prophylactic vaccines. Now, prophylactic vaccination induces protective and long-lasting antibody response which would also strengthened the natural moderate humoral response in people previously exposed to the virus.
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Affiliation(s)
- Ralph-Sydney Mboumba Bouassa
- Laboratoire De Virologie, Assistance Publique-Hôpitaux De Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France.,Laboratoire de virologie, Ecole Doctorale Régionale En Infectiologie Tropicale, Franceville, Gabon.,INSERM UMR U970 (Immunothérapie Et Traitement Anti-angiogénique En cancérologie), Paris Centre De Recherche Cardiovasculaire (PARCC), Hôpital Européen Georges Pompidou, AP-HP, Paris, France
| | - Hélène Péré
- Laboratoire De Virologie, Assistance Publique-Hôpitaux De Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France.,INSERM UMR U970 (Immunothérapie Et Traitement Anti-angiogénique En cancérologie), Paris Centre De Recherche Cardiovasculaire (PARCC), Hôpital Européen Georges Pompidou, AP-HP, Paris, France.,Faculté de Médecine, Université Paris Descartes, Paris, France
| | - Mohammad-Ali Jenabian
- Département Des Sciences Biologiques Et Centre De Recherche BioMed, Université Du Québec À Montréal (UQAM), Montreal, QC, Canada
| | - David Veyer
- Laboratoire De Virologie, Assistance Publique-Hôpitaux De Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France
| | - Jean-François Meye
- Service De Gynécologie Obstétrique, Centre Hospitalo-Universitaire d'Agondjé Et Faculté De Médecine De Libreville, Université Des Sciences De La Santé, Libreville, Gabon
| | - Antoine Touzé
- UMRINRA ISP 1282, Equipe Biologie Des Infections À Polyomavirus, Université De Tours, Tours, France
| | - Laurent Bélec
- Laboratoire De Virologie, Assistance Publique-Hôpitaux De Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France.,INSERM UMR U970 (Immunothérapie Et Traitement Anti-angiogénique En cancérologie), Paris Centre De Recherche Cardiovasculaire (PARCC), Hôpital Européen Georges Pompidou, AP-HP, Paris, France.,Faculté de Médecine, Université Paris Descartes, Paris, France
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32
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McClymont E, Ogilvie G, Albert A, Johnston A, Raboud J, Walmsley S, Lipsky N, Loutfy M, Trottier S, Smaill F, Yudin MH, Klein MB, Harris M, Wobeser W, Bitnun A, Kakkar F, Samson L, Brophy J, Karatzios C, Money D. Impact of quadrivalent HPV vaccine dose spacing on immunologic response in women living with HIV. Vaccine 2020; 38:3073-3078. [PMID: 32147300 DOI: 10.1016/j.vaccine.2020.02.075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 02/23/2020] [Accepted: 02/26/2020] [Indexed: 10/24/2022]
Abstract
HPV vaccination schedules have changed as evidence has supported reduced dosing and extended intervals. Women living with HIV (WLWH) represent an important population with no data on alternative dosing. Girls and WLWH received quadrivalent HPV (qHPV) vaccine in a pan-Canadian study of immunogenicity and efficacy. Serology was performed at months 0/2/7/12/18/24. Medical and sexual history was collected throughout. Linear regression was used to determine if spacing of doses was associated with peak antibody titer. Multivariable analyses demonstrated significant relationships between peak antibody titer and time to blood draw post last vaccine dose, naivety to the relevant HPV type, and HIV viral load for all qHPV types. There was a significant relationship between peak HPV16/18 antibody titer and age. Taking age, time to serology, CD4 cell count, CD4 nadir, HIV viral load, and HPV naivety into account, spacing of the three qHPV vaccine doses did not significantly impact peak antibody titers.
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Affiliation(s)
- Elisabeth McClymont
- Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
| | - Gina Ogilvie
- School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; Women's Health Research Institute, Vancouver, BC, Canada
| | - Arianne Albert
- Women's Health Research Institute, Vancouver, BC, Canada
| | - Angela Johnston
- Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Janet Raboud
- Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Sharon Walmsley
- Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Nancy Lipsky
- Women's Health Research Institute, Vancouver, BC, Canada
| | - Mona Loutfy
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON, Canada
| | - Sylvie Trottier
- Infectious Diseases Research Centre - Université Laval, Québec City, QC, Canada
| | - Fiona Smaill
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Mark H Yudin
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON, Canada; Department of Obstetrics and Gynecology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada
| | | | - Marianne Harris
- British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
| | - Wendy Wobeser
- Departments of Public Health and Biomedical & Molecular Sciences, Queen's University, Kingston, ON, Canada
| | - Ari Bitnun
- Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, ON, Canada
| | - Fatima Kakkar
- Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada; Centre Maternel et Infantile sur le SIDA, CHU Sainte-Justine, Montreal, QC, Canada
| | - Lindy Samson
- Department of Paediatrics, University of Ottawa, Ottawa, ON, Canada
| | - Jason Brophy
- Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada
| | - Christos Karatzios
- Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC, Canada; Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Deborah Money
- Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
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Mariz FC, Bender N, Anantharaman D, Basu P, Bhatla N, Pillai MR, Prabhu PR, Sankaranarayanan R, Eriksson T, Pawlita M, Prager K, Sehr P, Waterboer T, Müller M, Lehtinen M. Peak neutralizing and cross-neutralizing antibody levels to human papillomavirus types 6/16/18/31/33/45/52/58 induced by bivalent and quadrivalent HPV vaccines. NPJ Vaccines 2020; 5:14. [PMID: 32128255 PMCID: PMC7021830 DOI: 10.1038/s41541-020-0165-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 01/27/2020] [Indexed: 11/21/2022] Open
Abstract
We performed an independent comparison of neutralizing and cross-neutralizing antibody (ab) levels seven months after initiation of three-dose, six-month vaccination schedules with the bivalent and quadrivalent human papillomavirus (HPV) vaccines in adolescent Finnish and Indian females, respectively. We used a semi-automated Pseudovirion-Based Neutralization Assay and observed significantly higher HPV16/18 peak ab-levels in bivalent as compared to quadrivalent vaccine recipients. Bivalent vaccine induced cross-neutralizing HPV31/33/45/52/58 antibodies significantly more frequently and to higher levels than the quadrivalent vaccine. The correlation of bivalent vaccine-induced HPV45 ab-levels with HPV16/18 ab-levels was stronger than that of corresponding quadrivalent vaccine-induced ab-levels, suggesting a qualitatively different cross-reactive response. Our findings on the comparison of the immunogenicity of two HPV vaccine tested in two different populations indicate that further head-to-head studies are warranted.
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Affiliation(s)
- Filipe Colaço Mariz
- Tumorvirus-Specific Vaccination Strategies, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany
| | - Noemi Bender
- Infections and Cancer Epidemiology, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany
| | - Devasena Anantharaman
- Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, 695014 Kerala India
| | - Partha Basu
- Screening Group, International Agency for Research on Cancer (IARC), 69008 Lyon, France
| | - Neerja Bhatla
- All India Institute of Medical Sciences, 110029 New Delhi, India
| | | | - Priya R. Prabhu
- Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, 695014 Kerala India
| | - Rengaswamy Sankaranarayanan
- Research Triangle Institute International India, 6th Floor, Pullman Commercial Tower, Aero City, 110037 New Delhi India
| | | | - Michael Pawlita
- Infections and Cancer Epidemiology, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany
| | - Kristina Prager
- Infections and Cancer Epidemiology, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany
| | - Peter Sehr
- EMBL-DKFZ Chemical Biology Core Facility, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
| | - Tim Waterboer
- Infections and Cancer Epidemiology, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany
| | - Martin Müller
- Tumorvirus-Specific Vaccination Strategies, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany
| | - Matti Lehtinen
- Infections and Cancer Epidemiology, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany
- Karolinska Institute, 17177 Stockholm, Sweden
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Smalley Rumfield C, Roller N, Pellom ST, Schlom J, Jochems C. Therapeutic Vaccines for HPV-Associated Malignancies. Immunotargets Ther 2020; 9:167-200. [PMID: 33117742 PMCID: PMC7549137 DOI: 10.2147/itt.s273327] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 09/03/2020] [Indexed: 12/13/2022] Open
Abstract
Human papillomavirus (HPV)-related malignancies are responsible for almost all cases of cervical cancer in women, and over 50% of all cases of head and neck carcinoma. Worldwide, HPV-positive malignancies account for 4.5% of the global cancer burden, or over 600,000 cases per year. HPV infection is a pressing public health issue, as more than 80% of all individuals have been exposed to HPV by age 50, representing an important target for vaccine development to reduce the incidence of cancer and the economic cost of HPV-related health issues. The approval of Gardasil® as a prophylactic vaccine for high-risk HPV 16 and 18 and low-risk HPV6 and 11 for people aged 11-26 in 2006, and of Cervarix® in 2009, revolutionized the field and has since reduced HPV infection in young populations. Unfortunately, prophylactic vaccination does not induce immunity in those with established HPV infections or HPV-induced neoplasms, and there are currently no therapeutic HPV vaccines approved by the US Food and Drug Administration. This comprehensive review will detail the progress made in the development of therapeutic vaccines against high-risk HPV types, and potential combinations with other immunotherapeutic agents for more efficient and rational designs of combination treatments for HPV-associated malignancies.
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Affiliation(s)
- Claire Smalley Rumfield
- Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Nicholas Roller
- Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Samuel Troy Pellom
- Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Jeffrey Schlom
- Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Correspondence: Jeffrey Schlom Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Room 8B09, Bethesda, MD20892, USATel +1 240-858-3463Fax +1 240-541-4558 Email
| | - Caroline Jochems
- Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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35
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Comparative analysis of human papillomavirus type 6 complete genomes originated from head and neck and anogenital disorders. INFECTION GENETICS AND EVOLUTION 2019; 71:140-150. [PMID: 30905772 DOI: 10.1016/j.meegid.2019.03.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 01/20/2019] [Accepted: 03/20/2019] [Indexed: 01/12/2023]
Abstract
It is increasingly recognized that fundamental differences exist between high-risk and low-risk human papillomavirus (HPV) genotypes regarding interactions with the host. This study aims to join the recently emerging efforts to uncover these differences at the complete genome level and to study how they may influence the disease caused. Sixteen samples of thirteen patients with various HPV6-mediated benign mucosal disorders (nine recurrent respiratory papillomatoses with 2-8 recurrences, one condyloma acuminatum and three premalignant lesions of the genital mucosa) were sampled to determine the complete virus genomes. We collected the 197 HPV6 complete genomes deposited in the GenBank for cluster analysis to determine (sub)lineages. Genome polymorphisms were determined against the reference sequences of the (sub)lineages. Genome polymorphisms of the long control region (LCR) were tested for putative transcription factor binding sites; their functional analysis was performed by transient transfection of cloned whole LCRs into HEp-2 cells using a luciferase reporter system. Genomes from the same patients were always identical. Three, nine and one patients carried HPV6 lineage A, sublineage B1 and B2 variants, respectively. The three lineage A sequences were highly similar to each other, but distinct from the reference genome. A unique non-synonymous single nucleotide polymorphism (SNP) was found in the E5a open reading frame (ORF). Sublineage B1 genomes were more diverse, exhibited unique non-synonymous SNPs in the LCR and the E2/E4, L1, L2 ORFs. LCR activity of lineage A and sublineage B1 differed significantly; activity of one sublineage B1 LCR exhibiting two unique SNPs was significantly higher than that of other B1 LCR variants, close to the mean of LCR activities of lineage A variants. Different HPV6 lineages showed marked differences in variability patterns of the different genome regions. This may be involved in the differences in their distribution in different diseases or patient populations.
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36
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Dadar M, Chakraborty S, Dhama K, Prasad M, Khandia R, Hassan S, Munjal A, Tiwari R, Karthik K, Kumar D, Iqbal HMN, Chaicumpa W. Advances in Designing and Developing Vaccines, Drugs and Therapeutic Approaches to Counter Human Papilloma Virus. Front Immunol 2018; 9:2478. [PMID: 30483247 PMCID: PMC6240620 DOI: 10.3389/fimmu.2018.02478] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 10/08/2018] [Indexed: 02/05/2023] Open
Abstract
Human papillomavirus (HPV) is a viral infection with skin-to-skin based transmission mode. HPV annually caused over 500,000 cancer cases including cervical, anogenital and oropharyngeal cancer among others. HPV vaccination has become a public-health concern, worldwide, to prevent the cases of HPV infections including precancerous lesions, cervical cancers, and genital warts especially in adolescent female and male population by launching national programs with international alliances. Currently, available prophylactic and therapeutic vaccines are expensive to be used in developing countries for vaccination programs. The recent progress in immunotherapy, biotechnology, recombinant DNA technology and molecular biology along with alternative and complementary medicinal systems have paved novel ways and valuable opportunities to design and develop effective prophylactic and therapeutic vaccines, drugs and treatment approach to counter HPV effectively. Exploration and more researches on such advances could result in the gradual reduction in the incidences of HPV cases across the world. The present review presents a current global scenario and futuristic prospects of the advanced prophylactic and therapeutic approaches against HPV along with recent patents coverage of the progress and advances in drugs, vaccines and therapeutic regimens to effectively combat HPV infections and its cancerous conditions.
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Affiliation(s)
- Maryam Dadar
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran
| | - Sandip Chakraborty
- Department of Veterinary Microbiology, College of Veterinary Sciences and Animal Husbandry, West Tripura, India
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Minakshi Prasad
- Department of Animal Biotechnology, LLR University of Veterinary and Animal Sciences, Hisar, India
| | - Rekha Khandia
- Department of Genetics, Barkatullah University, Bhopal, India
| | - Sameer Hassan
- Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chennai, India
| | - Ashok Munjal
- Department of Genetics, Barkatullah University, Bhopal, India
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, U P Pt. Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwavidyalay Evum Go-Anusandhan Sansthan, Mathura, India
| | - Kumaragurubaran Karthik
- Central University Laboratory, Tamil Nadu Veterinary and Animal Sciences University, Chennai, India
| | - Deepak Kumar
- Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Hafiz M. N. Iqbal
- Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey, Mexico
| | - Wanpen Chaicumpa
- Department of Parasitology, Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Faculty of Medicine SIriraj Hospital, Mahidol University, Bangkok, Thailand
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Yang MY, Son JH, Kim GW, Kim HS, Ko HC, Kim MB, Lim KM, Kim BS. Quadrivalent human papilloma virus vaccine for the treatment of multiple warts: a retrospective analysis of 30 patients. J DERMATOL TREAT 2018; 30:405-409. [PMID: 30232912 DOI: 10.1080/09546634.2018.1527006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Background: Various therapeutic modalities have been implemented for wart treatment, with limited efficacy. Recently, resistant warts treated using quadrivalent human papilloma virus (HPV) vaccine have been reported, although original articles on the efficacy of quadrivalent HPV vaccine on warts are rare. Objective: We performed the present study to evaluate the efficacy of quadrivalent HPV vaccine in the treatment of multiple warts. Methods: We retrospectively reviewed 30 patients from our centers. Patient demographics, clinical features such as duration of disease, number and location of lesions, therapeutic response, and adverse reactions were assessed. Results: Regarding therapeutic response, 14 patients (46.67%) showed "Complete response", 5 (16.67%) showed "Partial response", and 11 (36.67%) showed "No response". There were no statistically significant differences in sex, age, disease duration, and lesion number and location between the three groups divided by treatment response. No severe adverse events after quadrivalent HPV vaccination were noted. Conclusion: The advantage of quadrivalent HPV vaccine in the treatment of warts is that it is more convenient and less painful. HPV vaccine might be a good alternative to conventional destructive methods for incompetent cases such as those including multiple warts, dangerous lesion locations, and uncooperative patients.
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Affiliation(s)
- Min-Young Yang
- a Department of Dermatology, College of Medicine , Pusan National University , Busan , Korea.,b Biomedical Research Institute , Pusan National University Hospital , Busan , Korea
| | - Jin-Hwa Son
- a Department of Dermatology, College of Medicine , Pusan National University , Busan , Korea.,b Biomedical Research Institute , Pusan National University Hospital , Busan , Korea
| | - Gun-Wook Kim
- a Department of Dermatology, College of Medicine , Pusan National University , Busan , Korea.,b Biomedical Research Institute , Pusan National University Hospital , Busan , Korea
| | - Hoon-Soo Kim
- a Department of Dermatology, College of Medicine , Pusan National University , Busan , Korea.,b Biomedical Research Institute , Pusan National University Hospital , Busan , Korea
| | - Hyun-Chang Ko
- a Department of Dermatology, College of Medicine , Pusan National University , Busan , Korea
| | - Moon-Bum Kim
- a Department of Dermatology, College of Medicine , Pusan National University , Busan , Korea.,b Biomedical Research Institute , Pusan National University Hospital , Busan , Korea
| | - Kyung-Min Lim
- c Department of Nursing Science , Dongju College , Busan , Korea
| | - Byung-Soo Kim
- a Department of Dermatology, College of Medicine , Pusan National University , Busan , Korea.,b Biomedical Research Institute , Pusan National University Hospital , Busan , Korea
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Minkner R, Baba R, Kurosawa Y, Suzuki S, Kato T, Kobayashi S, Park EY. Purification of human papillomavirus-like particles expressed in silkworm using a Bombyx mori nucleopolyhedrovirus bacmid expression system. J Chromatogr B Analyt Technol Biomed Life Sci 2018; 1096:39-47. [DOI: 10.1016/j.jchromb.2018.08.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 07/10/2018] [Accepted: 08/14/2018] [Indexed: 11/30/2022]
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Pinto LA, Dillner J, Beddows S, Unger ER. Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development. Vaccine 2018; 36:4792-4799. [PMID: 29361344 PMCID: PMC6050153 DOI: 10.1016/j.vaccine.2017.11.089] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 11/17/2017] [Indexed: 11/23/2022]
Abstract
When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials.
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MESH Headings
- Adolescent
- Antibodies, Neutralizing/blood
- Antibodies, Neutralizing/immunology
- Antibodies, Viral/blood
- Antibodies, Viral/immunology
- Child
- Clinical Trials as Topic
- Female
- Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage
- Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/immunology
- Humans
- Immunization Schedule
- Immunogenicity, Vaccine
- Male
- Mass Vaccination/standards
- Neutralization Tests/standards
- Papillomavirus Infections/prevention & control
- Papillomavirus Vaccines/administration & dosage
- Papillomavirus Vaccines/immunology
- Treatment Outcome
- Uterine Cervical Neoplasms/prevention & control
- World Health Organization
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Affiliation(s)
- Ligia A Pinto
- Vaccine, Cancer and Immunity Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
| | - Joakim Dillner
- Department of Laboratory Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
| | - Simon Beddows
- Virus Reference Department, Public Health England, London, UK.
| | - Elizabeth R Unger
- Chronic Viral Diseases Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
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40
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Mauz PS, Schäfer FA, Iftner T, Gonser P. HPV vaccination as preventive approach for recurrent respiratory papillomatosis - a 22-year retrospective clinical analysis. BMC Infect Dis 2018; 18:343. [PMID: 30041619 PMCID: PMC6057057 DOI: 10.1186/s12879-018-3260-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 07/17/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Recurrent respiratory papillomatosis (RRP) is a rare, benign disease of the aerodigestive tract, especially the larynx, caused by infection with the human papillomavirus (HPV) types 6 or 11. Current management focuses on surgical debulking with microdebrider of papillomatous lesions with or without concurrent adjuvant therapy, e.g. Cidofovir®. This retrospective study evaluates the results of patients treated at a department of the university clinic between 1990 and 2012 and compares the results of the conventional treatment with a new treatment approach using adjuvant vaccination with Gardasil®. METHODS A retrospective Kaplan Maier analysis of n = 24 patients diagnosed and treated with RPR was performed. The records were reviewed for gender, age at the time of first manifestation of disease and time to recurrence. RESULTS Only n = 2 (15.4%) of the n = 13 vaccinated patients developed a recurrence of the disease after a mean time of 54.9 months (SD: 9.5 months). All patients who were not vaccinated (n = 11; 100%) developed a relapse after a mean time of 12.3 months (SD: 9.72 months). CONCLUSION We propose that adjuvant HPV vaccination with Gardasil® might have a preventive effect in RRP by occluding new papilloma formation.
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Affiliation(s)
- Paul Stefan Mauz
- Department for Otolaryngology, Head and Neck Surgery, University Hospital of Tübingen, Eberhard Karls University Tübingen, Elfriede-Aulhorn-Str 5, DE-72076, Tübingen, Germany
| | | | - Thomas Iftner
- Division of Experimental Virology, Institute for Medical Virology, University Hospital of Tübingen, Eberhard Karls University Tübingen, DE-72076, Tübingen, Germany
| | - Phillipp Gonser
- Department for Otolaryngology, Head and Neck Surgery, University Hospital of Tübingen, Eberhard Karls University Tübingen, Elfriede-Aulhorn-Str 5, DE-72076, Tübingen, Germany.
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Arbyn M, Xu L, Simoens C, Martin‐Hirsch PPL. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev 2018; 5:CD009069. [PMID: 29740819 PMCID: PMC6494566 DOI: 10.1002/14651858.cd009069.pub3] [Citation(s) in RCA: 210] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. OBJECTIVES To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. SEARCH METHODS We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events. SELECTION CRITERIA Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine). DATA COLLECTION AND ANALYSIS We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets. MAIN RESULTS We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation.Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes.Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions.Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established.Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively). AUTHORS' CONCLUSIONS There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status.We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.
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Affiliation(s)
- Marc Arbyn
- SciensanoUnit of Cancer Epidemiology, Belgian Cancer CentreJuliette Wytsmanstreet 14BrusselsBelgiumB‐1050
| | - Lan Xu
- SciensanoUnit of Cancer Epidemiology, Belgian Cancer CentreJuliette Wytsmanstreet 14BrusselsBelgiumB‐1050
| | - Cindy Simoens
- University of AntwerpLaboratory of Cell Biology and HistologyGroenenborgerlaan 171AntwerpBelgiumB‐2020
| | - Pierre PL Martin‐Hirsch
- Royal Preston Hospital, Lancashire Teaching Hospital NHS TrustGynaecological Oncology UnitSharoe Green LaneFullwoodPrestonLancashireUKPR2 9HT
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Parker KH, Kemp TJ, Pan Y, Yang Z, Giuliano AR, Pinto LA. Evaluation of HPV-16 and HPV-18 specific antibody measurements in saliva collected in oral rinses and merocel® sponges. Vaccine 2018; 36:2705-2711. [PMID: 29631883 PMCID: PMC5953518 DOI: 10.1016/j.vaccine.2018.03.034] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 03/08/2018] [Accepted: 03/10/2018] [Indexed: 12/26/2022]
Abstract
BACKGROUND Current Human papillomavirus (HPV) L1 VLP vaccines protect against HPV-16 and HPV-18-associated cancers, in females and males. Although correlates of protection have not been identified, HPV-specific antibodies at sites of infection are thought to be the main mechanism of protection afforded by vaccination. Oral sampling has gained increased attention as a potential alternative to serum in monitoring immunity to vaccination and understanding local immunity in oral cancers. METHODS Serum was collected via venipuncture, and saliva was collected via oral rinses and Merocel® sponges from healthy volunteers: 16 unvaccinated females, 6 females (ages 24-41) and 6 mid-adult aged males (ages 27-45) recipients of three doses of the HPV-16/18/6/11 vaccine (Gardasil®). Mid-adult male vaccine trial participants were compared to female participants. Samples were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G levels by an L1 virus-like particle-based enzyme-linked immunosorbent assay (ELISA). RESULTS All vaccinated participants had detectable serum anti-HPV-16 and anti-HPV-18 antibodies. Optimal standard concentration range and sample serial dilutions for oral rinses were determined. The standard curve was not affected by the type of solution examined. Reproducibility of HPV-16 and HPV-18 antibody titers in mouthwash (overall CV < 10%) or in Merocel® extraction buffer was robust (CV < 13%). Excellent assay linearity (R2 > 0.9) was observed for sera spiked controls in both solutions. HPV-16 and HPV-18 specific antibodies were detectable in saliva from vaccine recipients, both in mouthwash and in Merocel® sponges but levels were several logs lower than those in serum. CONCLUSIONS This study confirms the application of HPV-16 and HPV-18 ELISAs currently used in sero-epidemiological studies of immunogenicity of HPV vaccines for use with oral samples. Oral samples may be a useful resource for the detection of HPV-16 and HPV-18-specific antibodies in saliva following vaccination.
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Affiliation(s)
- Katherine H Parker
- HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, USA
| | - Troy J Kemp
- HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, USA
| | - Yuanji Pan
- HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, USA
| | - Zhen Yang
- HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, USA
| | - Anna R Giuliano
- Center for Infection Research in Cancer, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Ligia A Pinto
- HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, USA.
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Louie KS, Dalel J, Reuter C, Bissett SL, Kleeman M, Ashdown-Barr L, Banwait R, Godi A, Sasieni P, Beddows S. Evaluation of Dried Blood Spots and Oral Fluids as Alternatives to Serum for Human Papillomavirus Antibody Surveillance. mSphere 2018; 3:e00043-18. [PMID: 29743199 PMCID: PMC5956145 DOI: 10.1128/msphere.00043-18] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 04/25/2018] [Indexed: 01/08/2023] Open
Abstract
Human papillomavirus (HPV) vaccination elicits high-titer genotype-specific antibody responses that are associated with a reduced risk of cervical disease caused by vaccine-incorporated genotypes. Our objective was to evaluate dried blood spots (DBSs) and oral mucosal transudate (OMT) as alternative samples to serum to confirm HPV vaccine antibody status. A study was carried out to evaluate the feasibility of detecting HPV16 and HPV18 antibodies in OMT, DBSs, and sera among women who self-reported being unvaccinated or fully vaccinated with the HPV vaccine. Serum had the highest sensitivity (100%) for detection of antibodies against both HPV16 and HPV18 but the lowest specificity, due to the detection of natural infection antibodies in 16% of unvaccinated women. Conversely, DBSs and OMT had lower sensitivity (96% and 82%, respectively) but high specificity (98%). We confirmed that these antibodies were functional (i.e., neutralizing) and that their detection was quantitatively reproducible and well correlated between sample types when normalized to IgG content. DBSs and OMT are appropriate alternative sample types for HPV vaccine surveillance. These alternative sample types warrant consideration for the purposes of cervical screening, diagnosis, and management, but more work will be needed to establish the stringent parameters required for such application.IMPORTANCE Human papillomavirus (HPV) is the causative agent of cervical and other anogenital cancers. HPV vaccination, primarily targeted at young girls before the age of sexual debut, is starting to demonstrate population-level declines in HPV infection and early disease associated with vaccine-incorporated genotypes. Monitoring young women for vaccine-specific antibody is important for vaccine surveillance and may be useful as an adjunct test within a cervical screening context. We evaluated serum, dried blood spots, and oral fluid as potential samples for such applications and report robust measures of diagnostic accuracy. This is the first time a direct comparison of alternative sample types has been made between vaccinated and unvaccinated women for the detection and quantitation of HPV antibodies.
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Affiliation(s)
- Karly S Louie
- Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
| | - Jama Dalel
- Virus Reference Department, Public Health England, London, United Kingdom
| | - Caroline Reuter
- Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
| | - Sara L Bissett
- Virus Reference Department, Public Health England, London, United Kingdom
| | - Michelle Kleeman
- Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
| | - Lesley Ashdown-Barr
- Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
| | - Rawinder Banwait
- Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
| | - Anna Godi
- Virus Reference Department, Public Health England, London, United Kingdom
| | - Peter Sasieni
- Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
| | - Simon Beddows
- Virus Reference Department, Public Health England, London, United Kingdom
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Proposal for cervical cancer screening in the era of HPV vaccination. Obstet Gynecol Sci 2018; 61:298-308. [PMID: 29780771 PMCID: PMC5956112 DOI: 10.5468/ogs.2018.61.3.298] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Revised: 09/19/2017] [Accepted: 10/20/2017] [Indexed: 01/23/2023] Open
Abstract
Eradication of cervical cancer involves the expansion of human papillomavirus (HPV) vaccine coverage and the development of efficient screening guidelines that take vaccination into account. In Korea, the HPV National Immunization Program was launched in 2016 and is expected to shift the prevalence of HPV genotypes in the country, among other effects. The experiences of another countries that implement national immunization programs should be applied to Korea. If HPV vaccines spread nationwide with broader coverage, after a few decades, cervical intraepithelial lesions or invasive cancer should become a rare disease, leading to a predictable decrease in the positive predictive value of cervical screening cytology. HPV testing is the primary screening tool for cervical cancer and has replaced traditional cytology-based guidelines. The current screening strategy in Korea does not differentiate women who have received complete vaccination from those who are unvaccinated. However, in the post-vaccination era, newly revised policies will be needed. We also discuss on how to increase the vaccination rate in adolescence.
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Stanley M. Tumour virus vaccines: hepatitis B virus and human papillomavirus. Philos Trans R Soc Lond B Biol Sci 2018; 372:rstb.2016.0268. [PMID: 28893935 DOI: 10.1098/rstb.2016.0268] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/09/2017] [Indexed: 12/11/2022] Open
Abstract
Two of the most important human oncogenic viruses are hepatitis B virus (HBV) and human papillomavirus (HPV). HBV infection has been preventable by vaccination since 1982; vaccination of neonates and infants is highly effective, resulting already in decreased rates of new infections, chronic liver disease and hepato-cellular carcinoma. Nonetheless, HBV remains a global public health problem with high rates of vertical transmission from mother to child in some regions. Prophylactic HPV vaccines composed of virus-like particles (VLPs) of the L1 capsid protein have been licensed since 2006/2007. These target infection by the oncogenic HPVs 16 and 18 (the cause of 70% of cervical cancers); a new vaccine licensed in 2014/2015 additionally targets HPVs 31, 33, 45, 52, 58. HPV vaccines are now included in the national immunization programmes in many countries, with young adolescent peri-pubertal girls the usual cohort for immunization. Population effectiveness in women is now being demonstrated in countries with high vaccine coverage with significant reductions in high-grade cervical intra-epithelial neoplasia (a surrogate for cervical cancer), genital warts and vaccine HPV type genoprevalence. Herd effects in young heterosexual men and older women are evident. Cancers caused by HBV and HPV should, in theory, be amenable to immunotherapies and various therapeutic vaccines for HPV in particular are in development and/or in clinical trial.This article is part of the themed issue 'Human oncogenic viruses'.
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Affiliation(s)
- Margaret Stanley
- Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
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Squamous Cell Papillomatosis in the Setting of Recurrent Respiratory Papillomatosis. Head Neck Pathol 2018; 13:235-238. [PMID: 29594918 PMCID: PMC6513981 DOI: 10.1007/s12105-018-0912-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 03/15/2018] [Indexed: 10/17/2022]
Abstract
A 23 year old male presented to the Otolaryngology clinic with 6 months of hoarseness and poor voice projection without improvement from speech therapy or medical anti-reflux medication. Upon examination he was found to have multiple polypoid lesions emanating from bilateral false vocal folds, left true vocal fold, and the anterior commissure. Biopsy and potassium titanyl phosphate (KTP) laser ablation with bevacizumab injection provided treatment and confirmed the clinical suspicion of squamous cell papilloma. Despite 3 years of treatment, the papillomatosis proved difficult to control, requiring a procedure approximately every 3 months. In an attempt to control the course of the disease the patient received a series of three bevacizumab and three cidofovir injections. Serial biopsies showed mild atypia within the squamous cell papillomas. Two separate biopsies confirmed presence of human papillomavirus (HPV) 6/11 via in situ hybridization with appropriate controls. There is promising research that the quadrivalent HPV (types 6, 11, 16, and 18) vaccine both reduces the disease burden in patients with active disease and reduces the incidence of recurrent respiratory papillomatosis (RRP). Other studies have shown that local immunologic dysregulation may play a role in RRP pathogenesis. Therefore new treatment options, to include PDL-1 blockade, offer hope in treating this benign condition with high morbidity and rare mortality.
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Huang T, Liu Y, Li Y, Liao Y, Shou Q, Zheng M, Liao X, Li R. Evaluation on the persistence of anti-HPV immune responses to the quadrivalent HPV vaccine in Chinese females and males: Up to 3.5 years of follow-up. Vaccine 2018; 36:1368-1374. [PMID: 29428178 DOI: 10.1016/j.vaccine.2018.02.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 01/17/2018] [Accepted: 02/01/2018] [Indexed: 11/17/2022]
Abstract
BACKGROUND This was an extension study of a randomized, double-blind, placebo-controlled immunogenicity and safety study of the quadrivalent human papillomavirus (qHPV) (HPV 6, 11, 16, and 18) vaccine conducted in Chinese female subjects aged 9-45 years and male subjects aged 9-15 years. To investigate the persistence of anti-HPV 6, -11, -16, and -18 responses among Chinese subjects, subjects enrolled in the base study were followed up at around month 42 (approximately 3.5 years after vaccination). METHODS Among 600 subjects enrolled in the base study, a total of 468 subjects consented for participation in the extension study. Anti-HPV 6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA) and total IgG Luminex immunoassay (IgG LIA). RESULTS Among the female subjects who received the qHPV vaccine, the proportions of subjects remained seropositive were high with both the cLIA and IgG LIA for HPV type 6, 11, and 16 through approximately 42 months following the first dose vaccination. For HPV 18, the seropositivity rate remained high as 82.0% with the IgG LIA, while it decreased to 53.6% with the cLIA, which was similar to the findings observed in other studies. The seropositivity rates remained high at month 42 for all qHPV types with both the cLIA and IgG LIA among the male subjects. CONCLUSIONS Administration of a 3-dose regimen of qHPV vaccine induces durable anti-HPV 6, anti-HPV 11, anti-HPV 16, and anti-HPV 18 responses among Chinese subjects for at least 3.5 years after vaccination. ClinicalTrials.gov registry:NCT01427777.
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Affiliation(s)
- Teng Huang
- Guangxi Center for Disease Control and Prevention, #18 Jin Zhou Road, Nanning 530028, Guangxi, PR China
| | - Youping Liu
- Wuzhou Center for Disease Control and Prevention, #3 Chun Hu Road, Wuzhou 543002, Guangxi, PR China
| | - Yanping Li
- Guangxi Center for Disease Control and Prevention, #18 Jin Zhou Road, Nanning 530028, Guangxi, PR China
| | - Yuqin Liao
- MSD R&D (China) Co., Ltd., #21 Rong Da Road, Beijing 100012, PR China
| | - Qiong Shou
- MSD R&D (China) Co., Ltd., #21 Rong Da Road, Beijing 100012, PR China
| | - Minghuan Zheng
- MSD R&D (China) Co., Ltd., #21 Rong Da Road, Beijing 100012, PR China
| | - Xueyan Liao
- MSD R&D (China) Co., Ltd., #21 Rong Da Road, Beijing 100012, PR China
| | - Rongcheng Li
- Guangxi Center for Disease Control and Prevention, #18 Jin Zhou Road, Nanning 530028, Guangxi, PR China.
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Widdice LE, Unger ER, Panicker G, Hoagland R, Callahan ST, Jackson LA, Berry AA, Kotloff K, Frey SE, Harrison CJ, Pahud BA, Edwards KM, Mulligan MJ, Sudman J, Bernstein DI. Antibody responses among adolescent females receiving two or three quadrivalent human papillomavirus vaccine doses at standard and prolonged intervals. Vaccine 2018; 36:881-889. [PMID: 29306506 PMCID: PMC6055998 DOI: 10.1016/j.vaccine.2017.12.042] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2017] [Revised: 11/21/2017] [Accepted: 12/07/2017] [Indexed: 01/15/2023]
Abstract
BACKGROUND The originally recommended dosing schedule, 0, 2, 6 months, for the 3-dose quadrivalent human papillomavirus vaccine (4vHPV) was often not followed, resulting in longer than recommended intervals between doses and interest in the effect of prolonged intervals. Recent two-dose recommendations require investigations into the effect of delaying dose 2. METHODS This multi-site, prospective study enrolled healthy 9-17 year old girls (n = 1321) on the day of or within 28 days following a third dose of 4vHPV vaccination. Antibody titers to 4vHPV types were measured at one and six months post-dose 3 from all participants and post-dose 2 from participants who were on time for dose 3. To compare antibody responses, participants were categorized into groups: second and third doses on time (control group); on-time dose 2, substantially late dose 3 (group 2); substantially late dose 2, on-time dose 3 (group 3); both doses substantially late (group 4). Analyses compared age-adjusted geometric mean titers (GMTs) at one-month and six-months post-dose 3, effect of delaying the second dose, and two versus three doses as well as post-dose 2 GMTs, stratified by age. RESULTS Compared to on-time dosing, one-month post-dose 3 GMTs were non-inferior in groups 2, 3, and 4 and were superior in group 2. Six month post-dose 3 GMTs were superior in groups 2, 3, and 4 for each genotype, except HPV 18 in group 3. Age-adjusted post does 2 titers were significantly lower than post-dose 3 titers when dose 2 was on time but were significantly higher when dose 2 was substantially late. Participants ≥15 years old had no difference in post-dose 2 titers compared to <15 year olds when dose 2 was substantially delayed. CONCLUSIONS Prolonged intervals between doses do not appear to diminish and may enhance antibody response to 4vHPV. ClinicalTrials.gov (NCT00524745).
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Affiliation(s)
- Lea E Widdice
- Division of Adolescent and Transition Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 4000, Cincinnati, OH 45229, United States.
| | - Elizabeth R Unger
- Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, United States.
| | - Gitika Panicker
- Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, United States.
| | - Rebecca Hoagland
- Cota Enterprises, Inc., 16570 46th Street, McLouth, KS 66054, United States.
| | - S Todd Callahan
- Division of Adolescent and Young Adult Health, Vanderbilt University, 719 Thompson Lane, Suite 36300, Nashville, TN 37204, United States.
| | - Lisa A Jackson
- Group Health Research Institute, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101, United States.
| | - Andrea A Berry
- Division of Infectious Disease and Tropical Pediatrics, Center for Vaccine Development, Institute for Global Health, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF 480, Baltimore, MD 21201, United States.
| | - Karen Kotloff
- Division of Infectious Disease and Tropical Pediatrics, Center for Vaccine Development, Institute for Global Health, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF 480, Baltimore, MD 21201, United States.
| | - Sharon E Frey
- Division of Infectious Diseases, Allergy and Immunology, Saint Louis University, 1100 S. Grand Boulevard, St. Louis, MO 63104, United States.
| | - Christopher J Harrison
- Division of Pediatric Infectious Diseases, Children's Mercy - Kansas City, 2401 Gillham Road, MO 64108, United States.
| | - Barbara A Pahud
- Division of Pediatric Infectious Diseases, Children's Mercy - Kansas City, 2401 Gillham Road, MO 64108, United States.
| | - Kathryn M Edwards
- Division of Pediatric Infectious Diseases, Vanderbilt Vaccine Research Program, D7227 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
| | - Mark J Mulligan
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court, Suite 200, Decatur, GA 30030, United States.
| | - Jon Sudman
- Kaiser Permanente Georgia, 200 Crescent Centre Parkway, Lower Level, Tucker, GA 30084, United States.
| | - David I Bernstein
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 6014, Cincinnati, OH 45229, United States.
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Jindal HA, Kaur A, Murugan S. Human papilloma virus vaccine for low and middle income countries: A step too soon? Hum Vaccin Immunother 2017; 13:2723-2725. [PMID: 28846491 DOI: 10.1080/21645515.2017.1358837] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Cervical Cancer is the most common genital cancer in women in India. Human papilloma virus (HPV) causes precancerous lesions that often develop into cervical cancer suggesting that cervical cancer has an infective etiology and is potentially preventable by preventing HPV infection through the use of HPV vaccines. The incidence in developing nations is largely under-reported due to large population size, poor and incomplete database. HPV vaccine is being considered for inclusion in the immunization schedule of developing countries. An effective surveillance system for a vaccine requires that the baseline incidence, prevalence, and mortality rates of cervical cancer are established for a given population. The lessons learnt from the polio vaccine must be applied to every vaccine being introduced for its optimal utilization. HPV vaccines might be used as a cost-effective scientific intervention to prevent cervical cancer but need to be combined with good screening methods in developing countries for a paradigm shift in the management of cervical cancer.
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Affiliation(s)
| | - Amanjot Kaur
- b Department of Obstetrics and Gynecology , PGIMER , Chandigarh , India
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Ewaisha R, Panicker G, Maranian P, Unger ER, Anderson KS. Serum Immune Profiling for Early Detection of Cervical Disease. Am J Cancer Res 2017; 7:3814-3823. [PMID: 29109779 PMCID: PMC5667406 DOI: 10.7150/thno.21098] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 07/09/2017] [Indexed: 12/25/2022] Open
Abstract
Background: The most recent (2012) worldwide estimates from International Agency for Research on Cancer indicate that approximately 528,000 new cases and 270,000 deaths per year are attributed to cervical cancer worldwide. The disease is preventable with HPV vaccination and with early detection and treatment of pre-invasive cervical intraepithelial neoplasia, CIN. Antibodies (Abs) to HPV proteins are under investigation as potential biomarkers for early detection. Methods: To detect circulating HPV-specific IgG Abs, we developed programmable protein arrays (NAPPA) that display the proteomes of two low-risk HPV types (HPV6 and 11) and ten oncogenic high-risk HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52 and 58). Arrays were probed with sera from women with CIN 0/I (n=78), CIN II/III (n=84), or invasive cervical cancer (ICC, n=83). Results: Abs to any early (E) HPV protein were detected less frequently in women with CIN 0/I (23.7%) than women with CIN II/III (39.0%) and ICC (46.1%, p<0.04). Of the E Abs, anti-E7 Abs were the most frequently detected (6.6%, 19.5%, and 30.3%, respectively). The least frequently detected Abs were E1 and E2-Abs in CIN 0/I (1.3%) and E1-Abs in CIN II/III (1.2%) and ICC (7.9%). HPV16-specific Abs correlated with HPV16 DNA detected in the cervix in 0% of CIN 0/I, 21.2% of CIN II/III, and 45.5% of ICC. A significant number (29 - 73%) of E4, E7, L1, and L2 Abs had cross-reactivity between HPV types. Conclusion: HPV protein arrays provide a valuable high-throughput tool for measuring the breadth, specificity, and heterogeneity of the serologic response to HPV in cervical disease.
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