|
1
|
Kang M, Marks KM, Cox AL, Sherman KE. An efficient vaccine clinical trial: ACTG A5379 hepatitis B vaccine trial in persons with HIV. Vaccine 2025; 55:127028. [PMID: 40147293 PMCID: PMC12078002 DOI: 10.1016/j.vaccine.2025.127028] [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: 09/03/2024] [Revised: 02/07/2025] [Accepted: 03/13/2025] [Indexed: 03/29/2025]
Abstract
Clinical trial designs that address multiple questions more efficiently are desirable. When we designed a hepatitis B vaccine trial to assess seroprotective outcomes in persons with HIV (PWH), we aimed for an efficient design that addressed three primary objectives in two study populations. The study focused on: PWH who did not respond to prior HBV vaccination, and PWH with no known history of HBV vaccination. Whereas one vaccine regimen was studied in the vaccine-naïve participants, multiple interventions were considered for those with prior nonresponse, with two different vaccines and two dosing schedules. Several features of the trial design required statistical considerations related to multiple testing: (1) assessment of vaccine response in two study populations under one trial, (2) comparisons among multiple treatment arms, and (3) sequential repeated significance tests in interim data monitoring. We describe the features aimed to gain statistical and administrative efficiencies, including reduction in the study sample size of 12 %. We also describe how we controlled type I error and planned interim data monitoring, and highlight the time lag issue due to the laboratory-based immunogenicity endpoint in this international, multi-center trial (NCT04193189).
Collapse
Affiliation(s)
- Minhee Kang
- Center for Biostatistics in AIDS Research in the Department of Biostatistics, Harvard T.H. Chan School of Public Health, 651 Huntington Ave, Boston, MA 02115, USA.
| | - Kristen M Marks
- Division of Infectious Diseases, Weill Cornell Medicine, 525 East 68th Street, New York, NY 10065, USA.
| | - Andrea L Cox
- Division of Infectious Diseases, Johns Hopkins School of Medicine, John Rangos Research Building, 855 N. Wolfe St, Baltimore, MD 21205, USA.
| | - Kenneth E Sherman
- Gastroenterology Division, Massachusetts General Hospital-Harvard Medical School, 15 Parkman Street, Boston, MA 02114, USA.
| |
Collapse
|
|
2
|
Bieńkowski C, Żak Z, Fijołek F, Cholewik M, Stępień M, Skrzat-Klapaczyńska A, Kowalska JD. Immunological and Clinical Responses to Vaccinations among Adults Living with HIV. Life (Basel) 2024; 14:540. [PMID: 38792562 PMCID: PMC11122059 DOI: 10.3390/life14050540] [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: 03/04/2024] [Revised: 04/07/2024] [Accepted: 04/17/2024] [Indexed: 05/26/2024] Open
Abstract
People living with human immunodeficiency virus (HIV) are at higher risk of morbidity and mortality due to vaccine-preventable diseases. At the same time, they are less likely to respond to vaccinations, and might have a higher rate of vaccine adverse event and faster waning of protective effect. International and national guidelines emphasize the importance of vaccinating people living with HIV against respiratory system disease pathogens including seasonal influenza, Streptococcus pneumoniae, and COVID-19, as well as against sexually transmitted infections, i.e., Hepatitis A and B (HAV, HBV) and human papillomavirus (HPV). This narrative review aims to provide a comprehensive examination of the current knowledge regarding the immune and clinical responses elicited by vaccinations in the older adult population living with HIV.
Collapse
Affiliation(s)
- Carlo Bieńkowski
- Hospital for Infectious Diseases in Warsaw, 01-201 Warsaw, Poland; (F.F.); (A.S.-K.); (J.D.K.)
- Department of Adults’ Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland
| | - Zuzanna Żak
- Department of Internal Medicine, Endocrinology, and Diabetes, Medical University of Warsaw, 01-201 Warsaw, Poland;
| | - Filip Fijołek
- Hospital for Infectious Diseases in Warsaw, 01-201 Warsaw, Poland; (F.F.); (A.S.-K.); (J.D.K.)
- Department of Adults’ Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland
| | - Martyna Cholewik
- Student’s Scientific Group at the Department of Adults’ Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland; (M.C.); (M.S.)
| | - Maciej Stępień
- Student’s Scientific Group at the Department of Adults’ Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland; (M.C.); (M.S.)
| | - Agata Skrzat-Klapaczyńska
- Hospital for Infectious Diseases in Warsaw, 01-201 Warsaw, Poland; (F.F.); (A.S.-K.); (J.D.K.)
- Department of Adults’ Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland
| | - Justyna D. Kowalska
- Hospital for Infectious Diseases in Warsaw, 01-201 Warsaw, Poland; (F.F.); (A.S.-K.); (J.D.K.)
- Department of Adults’ Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland
| |
Collapse
|
|
3
|
Marks KM, Kang M, Umbleja T, Avihingsanon A, Sugandhavesa P, Cox AL, Vigil K, Perazzo H, Price JC, Katsidzira L, Vernon C, Alston-Smith B, Sherman KE. Immunogenicity and Safety of Hepatitis B Virus (HBV) Vaccine With a Toll-Like Receptor 9 Agonist Adjuvant in HBV Vaccine-Naïve People With Human Immunodeficiency Virus. Clin Infect Dis 2023; 77:414-418. [PMID: 37017075 PMCID: PMC10681652 DOI: 10.1093/cid/ciad201] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 03/24/2023] [Accepted: 03/31/2023] [Indexed: 04/06/2023] Open
Abstract
In this international, multicenter open-label study (ACTG A5379) of HepB-CpG vaccine in people with human immunodeficiency virus (HIV) without prior hepatitis B virus (HBV) vaccination, all 68 participants achieved HBV seroprotective titers after the 3-dose series in the primary analysis. No unexpected safety issues were observed.
Collapse
Affiliation(s)
- Kristen M Marks
- Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA
| | - Minhee Kang
- Center for Biostatistics in AIDS Research in the Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Triin Umbleja
- Center for Biostatistics in AIDS Research in the Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Anchalee Avihingsanon
- HIV-NAT, Thai Red Cross AIDS Research Centre and CE in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | - Andrea L Cox
- Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland, USA
| | - Karen Vigil
- Division of Infectious Diseases, McGovern Medical School, University of Texas, Houston, Texas, USA
| | - Hugo Perazzo
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Jennifer C Price
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Leolin Katsidzira
- Internal Medicine Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | | | - Beverly Alston-Smith
- Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| |
Collapse
|
|
4
|
Tian Y, Hua W, Wu Y, Zhang T, Wang W, Wu H, Guo C, Huang X. Immune Response to Hepatitis B Virus Vaccine Among People Living With HIV: A Meta-Analysis. Front Immunol 2022; 12:745541. [PMID: 35003061 PMCID: PMC8728056 DOI: 10.3389/fimmu.2021.745541] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 12/06/2021] [Indexed: 12/18/2022] Open
Abstract
Background There is conflicting evidence about whether a double dose of the hepatitis B virus (HBV) vaccine induces better immunity than the standard-dose vaccine for people living with HIV (PLWH). This study provides a meta-analysis that summarizes the efficacy of HBV vaccine regimens among HIV-infected patients, clarifying the role of particular factors such as dose and frequency of vaccination in vaccine responsiveness and highlighting the need for evidence-based practice to assess HBV vaccination among PLWH. Methods Randomized clinical trials (RCTs) and prospective studies reporting vaccination response rates among PLWH were found through a search of PubMed, Cochrane, and the Web of Science. The key outcome was vaccine response. A random-effects model was used to estimate the pooled response rate. Subgroup analysis was conducted to evaluate key factors and explore sources of heterogeneity. Possible biases were assessed using quality and publication bias assessment. Results Eligible studies included controlled trials that examined the effects of 17 interventional studies with 1,821 participants. Among PLWH who received the HBV vaccine, the pooled response rate of HBV vaccination was 71.5% (95% CI 64.0%-77.9%, p < 0.001). Compared with the standard dose (65.5%, 95% CI 53.1%-76.1%), the double dose (75.2%, 95% CI 66.2%-82.5%) was associated with a better response rate [Q(1) = 19.617, p < 0.001]. When stratified by schedule, the four-dose schedule (89.7%, 95% CI 83.1%-93.9%) had a higher response rate than the three-dose schedule (63.3%, 95% CI 56.6%-69.4%) and the difference was significant [Q(1) = 88.305, p < 0.001]. PLWH with higher CD4+ T-cell counts (>500 cells/mm3) at the time of vaccination had better response rates [Q(1) = 88.305, p < 0.001]. Conclusions In this meta-analysis, the double dose of the HBV vaccine and multiple injections were associated with better immune responses than the standard HBV vaccine regimen in PLWH. Higher seroconversion rates were observed in PLWH with high CD4+ T-cell levels, indicating that individuals infected with HIV should receive the HBV vaccine as soon as possible after diagnosis. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/.
Collapse
Affiliation(s)
- Yakun Tian
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Wei Hua
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yaxin Wu
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Tong Zhang
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Wen Wang
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Hao Wu
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Caiping Guo
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaojie Huang
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
5
|
Chaiwarith R, Praparattanapan J, Kotarathititum W, Wipasa J, Chaiklang K, Supparatpinyo K. Higher rate of long-term serologic response of four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: 4-year follow-up of a randomised controlled trial. AIDS Res Ther 2019; 16:33. [PMID: 31711528 PMCID: PMC6844022 DOI: 10.1186/s12981-019-0249-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 10/25/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND We previously reported that four doses or four double doses of hepatitis B vaccination regimens could not significantly increase a response rate compared with standard doses. However, the antibody levels were higher in the four doses and four double doses groups. This study followed those patients for at least 3 years and aimed to evaluate the immunogenicity of the three vaccination regimens. METHODS HIV-infected adults who had CD4+ cell counts > 200 cells/mm3, undetectable plasma HIV-1 RNA, and negative for all hepatitis B virus markers were randomly assigned to receive one of three recombinant vaccines (Hepavax-Gene® Berna, Korea) regimens: 20 μg IM at months 0, 1, and 6 (standard doses group, n = 44), 20 μg IM at months 0, 1, 2, 6 (four doses group, n = 44), or 40 μg IM at months 0, 1, 2, and 6 (four double doses group, n = 44) between February 2011 and May 4, 2012. Of 132 participants, 126 were evaluated from August 2015 to January 2016; 42 in the standard doses, 43 in the four doses, and 41 in the four double doses groups. RESULTS At a median duration of 49.7 months (range 46.7-53.7) after completion of the primary vaccination schedule, the percentages of responders with anti-HBs ≥ 10 mIU/mL were 57.1% (95% CI 41.5-72.8%) in the standard doses group; 76.7% (95% CI 63.6-89.9%) in the four doses group (P = 0.067 vs. the standard doses group); and 80.5% (95% CI 67.8-93.2%) in the four double doses group (P = 0.033 vs. the standard doses group). Factors associated with a responder were the vaccination schedule (either four doses or four double doses groups) and a younger age. CONCLUSIONS Despite the highly effectiveness of the standard hepatitis B vaccination regimen at 6 months after completion, the long-term immunogenicity was lower than the four double doses regimen among HIV-infected adults with CD4+ cell counts > 200 cells/mm3 and undetectable plasma HIV-1 RNA. The standard vaccination regimen may not be the best strategy to provide long-term immune response against hepatitis B virus among HIV-infected individuals. Trial registration NCT1289106, NCT02713620.
Collapse
|
|
6
|
Chang L, Lim BCW, Flaherty GT, Torresi J. Travel vaccination recommendations and infection risk in HIV-positive travellers. J Travel Med 2019; 26:5486056. [PMID: 31066446 DOI: 10.1093/jtm/taz034] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/26/2019] [Accepted: 04/30/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND With the advent of highly active antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) it has become possible for people with HIV to travel to destinations that may place them at risk of a number of infectious diseases. Prevention of infections by vaccination is therefore of paramount importance for these travellers. However, vaccine responsiveness in HIV-positive individuals is not infrequently reduced compared to HIV-negative individuals. An understanding of the expected immune responses to vaccines in HIV-positive travellers is therefore important in planning the best approach to a pretravel consultation. METHODS A PubMed search was performed on HIV or acquired immune deficiency syndrome together with a search for specific vaccines. Review of the literature was performed to develop recommendations on vaccinations for HIV-positive travellers to high-risk destinations. RESULTS The immune responses to several vaccines are reduced in HIV-positive people. In the case of vaccines for hepatitis A, hepatitis B, influenza, pneumococcus, meningococcus and yellow fever there is a good body of data in the literature showing reduced immune responsiveness and also to help guide appropriate vaccination strategies. For other vaccines like Japanese encephalitis, rabies, typhoid fever, polio and cholera the data are not as robust; however, it is still possible to gain some understanding of the reduced responses seen with these vaccines. CONCLUSION This review provides a summary of the immunological responses to commonly used vaccines for the HIV-positive travellers. This information will help guide travel medicine practitioners in making decisions about vaccination and boosting of travellers with HIV.
Collapse
Affiliation(s)
- Lisa Chang
- Department of Microbiology, Dorevitch Pathology, Melbourne, Victoria, Australia
| | - Bryan Chang Wei Lim
- School of Medicine, National University of Ireland, Galway, Ireland.,School of Medicine, International Medical University, Kuala Lumpur, Malaysia
| | - Gerard T Flaherty
- School of Medicine, National University of Ireland, Galway, Ireland.,School of Medicine, International Medical University, Kuala Lumpur, Malaysia
| | - Joseph Torresi
- Department of Microbiology and Immunology, Peter Doherty Institute, The University of Melbourne, Parkville, Victoria, Australia
| |
Collapse
|
|
7
|
Zhao W, Zhao G, Zhang S, Wang X, Yu X, Wang B. Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant. Oncotarget 2018; 9:34213-34228. [PMID: 30344938 PMCID: PMC6188151 DOI: 10.18632/oncotarget.25789] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Accepted: 10/30/2017] [Indexed: 12/19/2022] Open
Abstract
Chronic hepatitis B virus (CHB) infection is a significant public threat. Current interferon-α (IFN-α) based therapies and anti-viral drugs have failed to clear the infection in the majority of CHB patients and animal models. In our previous study, we established a combined protocol that employed a 3-day pretreatment with granulocyte-macrophage colony stimulating factor (GM-CSF) prior to a standard HBV vaccine. It achieved a 90% reduction of HBsAg level in the HBsAg transgenic mouse model. This protocol, while effective, remains too complex for clinical use. In this study, we formulated a new regimen by combining GM-CSF, IFN-α and a recombinant HBV vaccine (GM-CSF/IFN-α/VACCINE) into a single preparation and tested its efficacy in a HBV infection model. After four vaccinations, both serum HBeAg and HBsAg were cleared, accompanied by a 95% reduction of HBV+ hepatocytes and the presence of a large number of infiltrating CD8+ T cells in the liver. Mechanistically these robust responses were initiated by a vaccine-induced conversion of CCR2-dependent CD11b+Ly6Chi monocytes into CD11b+CD11c+ DCs. This finding sheds light on the potential mechanism of action of the GM-CSF-based vaccine adjuvant and provides definable markers for clinical assessment during future testing of such highly potent vaccine protocols in HBV patients.
Collapse
Affiliation(s)
- Weidong Zhao
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Gan Zhao
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Shuren Zhang
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Xianzheng Wang
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Xueping Yu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Bin Wang
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| |
Collapse
|
|
8
|
Sherman KE, Peters MG, Thomas D. Human immunodeficiency virus and liver disease: A comprehensive update. Hepatol Commun 2017; 1:987-1001. [PMID: 30838978 PMCID: PMC5721407 DOI: 10.1002/hep4.1112] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 08/29/2017] [Accepted: 09/19/2017] [Indexed: 12/16/2022] Open
Abstract
Among persons living with human immunodeficiency virus (HIV) infection, liver disease remains a major cause of morbidity and mortality. While the etiologies are varied and often overlapping in the individual patient, the underlying mechanisms, including oxidative stress, direct activation of stellate cells, HIV interaction with hepatocytes, and bacterial translocation with systemic immune activation, seem to be unifying characteristics. Early and fully suppressive HIV antiretroviral therapy is a mainstay of management either before or concurrent with treatment of etiologic cofactors, including hepatitis C virus, hepatitis B virus, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Significant barriers to care that still exist include liver disease recognition, appropriate linkage to care, ongoing substance abuse, and psychiatric comorbidities in the HIV-infected population. Emerging issues in these patients include acute and chronic hepatitis E, underreported hepatitis D, and a rising incidence of hepatocellular carcinoma. (Hepatology Communications 2017;1:987-1001).
Collapse
|
|
9
|
Catherine FX, Piroth L. Hepatitis B virus vaccination in HIV-infected people: A review. Hum Vaccin Immunother 2017; 13:1-10. [PMID: 28267387 PMCID: PMC5489285 DOI: 10.1080/21645515.2016.1277844] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Revised: 12/16/2016] [Accepted: 12/24/2016] [Indexed: 12/21/2022] Open
Abstract
HBV immunization is highly recommended in people infected with HIV. However, the classical schedule used in the general population has been shown to be insufficient in people living with HIV. This review summarizes the main studies dealing with HBV vaccination in people living with HIV, depending on their baseline status (in particular, never vaccinated, already vaccinated, or with an isolated anti-HBc serological profile). It shows that reinforced 40µg intramuscular HBV vaccination schedules are now frequently recommended, either initially in people never vaccinated, or in the lack of an anamnestic response in other situations. Adjuvants cannot be currently recommended. Anti-HBs titers have to be checked 1 to 2 months following the last vaccine dose, and annually thereafter a booster is necessary if antiHBs titers decrease below 10 mIU/mL. In patients with a CD4 cell count <200/µL, guidelines recommend starting the vaccination regimen as soon as possible after HAART has been started.
Collapse
|
|
10
|
Eichinger KM, Resetar E, Orend J, Anderson K, Empey KM. Age predicts cytokine kinetics and innate immune cell activation following intranasal delivery of IFNγ and GM-CSF in a mouse model of RSV infection. Cytokine 2017; 97:25-37. [PMID: 28558308 DOI: 10.1016/j.cyto.2017.05.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 05/20/2017] [Accepted: 05/23/2017] [Indexed: 12/22/2022]
Abstract
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and is further associated with increased healthcare utilization and cost of care in the first years of life. Severe RSV disease during infancy has also been linked to the later development of allergic asthma, yet there remains no licensed RSV vaccine or effective treatment. Pre-clinical and clinical studies have shown that disease severity and development of allergic asthma are associated with differences in cytokine production. As a result, stimulation of the innate host immune response with immune potentiators is gaining attention for their prospective application in populations with limited immune responses to antigenic stimuli or against pathogens for which vaccines do not exist. Specifically, macrophage-activating cytokines such as interferon gamma (IFNγ) and granulocyte colony-stimulating factor (GM-CSF) are commercially available immune potentiators used to prevent infections in patients with chronic granulomatous disease and febrile neutropenia, respectively. Moreover, an increasing number of reports describe the protective function of IFNγ and GM-CSF as vaccine adjuvants. Although a positive correlation between cytokine production and age has previously been reported, little is known about age-dependent cytokine metabolism or immune activating responses in infant compared to adult lungs. Here we use a non-compartmental pharmacokinetic model in naïve and RSV-infected infant and adult BALB/c mice to determine the effect of age on IFNγ and GM-CSF elimination and innate cell activation following intranasal delivery.
Collapse
Affiliation(s)
- Katherine M Eichinger
- Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA; Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Erin Resetar
- Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jacob Orend
- Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA; Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA
| | - Kacey Anderson
- Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA; Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA
| | - Kerry M Empey
- Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA; Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA.
| |
Collapse
|
|
11
|
Fuster F, Vargas JI, Jensen D, Sarmiento V, Acuña P, Peirano F, Fuster F, Arab JP, Martínez F. CD4/CD8 ratio as a predictor of the response to HBV vaccination in HIV-positive patients: A prospective cohort study. Vaccine 2016; 34:1889-95. [PMID: 26945101 DOI: 10.1016/j.vaccine.2016.02.055] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 02/17/2016] [Accepted: 02/19/2016] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission mechanisms and thus coinfection is frequent. Active immunization against HBV is essential in HIV patients. Reports using standard and reinforced HBV vaccination schedules vary widely in seroconversion rates depending on the characteristics of the included patients. Regional data concerning HBV vaccination in HIV patients are scarce. We aim to determine the serological response to HBV vaccination using standard schedule in HIV-positive patients and to evaluate characteristics that predict seroconversion. MATERIALS AND METHODS We performed a single centre prospective study of HBV vaccination with standard schedule in HIV-positive patients. Adults with negative markers of HBV infection were included between November 2012 and December 2014. Anti-HBs titres were measured 4-8 weeks after completion of vaccination schedule. Clinical, laboratory values and HIV characteristics were analyzed to determine their association with seroconversion and adherence to the HBV vaccination schedule. RESULTS The study included 245 HIV-positive patients, 68.9% were male and the mean age was 42.1 years. A total of 80.7% of the patients had undetectable HIV viral loads, 86.1% had CD4 counts >200, and 94.7% were on HAART. The response to vaccination was positive in 62% (95% CI, 56-68%) and mean anti-HBs titres of 646 IU/ml. 85.5% of the responders had anti-HBs titres >100 IU/ml. An age less than 45 years, no tobacco use and a CD4/CD8 ratio >0.4 were associated with seroconversion in multivariate analysis. The seroconversion rates were 86% in the subgroup of patients who met these criteria. A total of 97.9% of the study population completed the vaccination schedule. CONCLUSION The CD4/CD8 ratio was the primary factor associated with positive serological conversion in the multivariate analysis. The seroconversion rates were higher in a selected group of patients who were particularly suitable for the use of the standard HBV vaccination schedule.
Collapse
Affiliation(s)
| | - Jose Ignacio Vargas
- Unidad de Hepatología, Hospital Gustavo Fricke, Chile; Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile; Servicio de Medicina Interna, Hospital Naval Almirante Nef, Chile.
| | - Daniela Jensen
- Servicio de Medicina Interna, Hospital Naval Almirante Nef, Chile; Escuela de Medicina, Universidad de Valparaíso, Chile
| | | | - Pedro Acuña
- Escuela de Medicina, Universidad Andrés Bello, Chile
| | | | - Felipe Fuster
- Escuela de Medicina, Universidad Del Desarrollo, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile
| | - Felipe Martínez
- Departamento de Salud Pública, Escuela de Medicina, Universidad de Valparaíso, Chile; Área de Investigación y Estudios Clínicos, Clínica Ciudad del Mar, Chile
| | | |
Collapse
|
|
12
|
Li Z, Wang G, Wang Y, Zhang C, Huang B, Li Q, Li L, Xue B, Ding P, Cai X, Wang C, Zhou EM. Immune responses of pigs immunized with a recombinant porcine reproductive and respiratory syndrome virus expressing porcine GM-CSF. Vet Immunol Immunopathol 2015; 168:40-8. [PMID: 26300317 DOI: 10.1016/j.vetimm.2015.08.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 07/27/2015] [Accepted: 08/10/2015] [Indexed: 10/23/2022]
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) has spread worldwide, causing huge economic losses to the swine industry. The current PRRSV vaccines have failed to provide broad protection against various strains. Granulocyte macrophage colony-stimulating factor (GM-CSF), an efficacious adjuvant, has been shown to enhance the immunogenicity of various vaccines. The purpose of this study was to construct a recombinant live attenuated PRRSV that expresses porcine GM-CSF (pGM-CSF) and evaluate the immune responses of pigs immunized with the recombinant virus. The results showed that the recombinant PRRSV was successfully rescued and had similar growth properties to parental virus grown in Marc-145 cells. The recombinant virus was stable for 10 passages in cell culture. Pigs intramuscularly immunized with the recombinant virus produced a similar humoral response to that elicited using parental virus. With regard to cell-mediated immunity assessed in peripheral blood, the recombinant virus induced higher proportion of CD4(+)CD8(+) double-positive T cells (DPT), higher IFN-γ level at 0 and 7 days post-challenge (DPC), and lower viremia at 21 DPC than pigs immunized with parental virus. These results indicate that recombinant PRRSV expressing pGM-CSF can induce a significant higher cellular immune response and reduce the persistent infection compared pigs vaccinated with the parental virus. This is first report of evaluation of immune response in pigs elicited by a recombinant live attenuated PRRSV expressing porcine GM-CSF. It may represent a novel strategy for future development of genetic engineered vaccines against PRRSV infection.
Collapse
Affiliation(s)
- Zhijun Li
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, China Ministry of Agriculture, Yangling, Shaanxi 712100, China
| | - Gang Wang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, Heilongjiang Province 150001, China
| | - Yan Wang
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, China Ministry of Agriculture, Yangling, Shaanxi 712100, China
| | - Chong Zhang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, Heilongjiang Province 150001, China
| | - Baicheng Huang
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, China Ministry of Agriculture, Yangling, Shaanxi 712100, China
| | - Qiongyi Li
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, China Ministry of Agriculture, Yangling, Shaanxi 712100, China
| | - Liangliang Li
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, China Ministry of Agriculture, Yangling, Shaanxi 712100, China
| | - Biyun Xue
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, China Ministry of Agriculture, Yangling, Shaanxi 712100, China
| | - Peiyang Ding
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, China Ministry of Agriculture, Yangling, Shaanxi 712100, China
| | - Xuehui Cai
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agriculture Science, Harbin, Heilongjiang Province 150001, China
| | - Chengbao Wang
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, China Ministry of Agriculture, Yangling, Shaanxi 712100, China.
| | - En-Min Zhou
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, China Ministry of Agriculture, Yangling, Shaanxi 712100, China.
| |
Collapse
|
|
13
|
Abstract
Hepatitis B and A account for considerable morbidity and mortality worldwide. Immunization is the most effective means of preventing hepatitis B and A. However, the immune response to both hepatitis vaccines seems to be reduced in HIV-infected subjects. The aim of this review was to analyze the immunogenicity, safety, long-term protection and current recommendations of hepatitis B and A vaccination among HIV-infected adults. The factors most frequently associated with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those related to immunosuppression (CD4 level and HIV RNA viral load) and to the frequency of administration and/or the amount of antigenic load per dose. The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination. In terms of safety, there is no evidence of more, or different, adverse effects compared with HIV-free individuals. Despite literature-based advice on the administration of alternative schedules, revaccination after the failure of primary vaccination, and the need for periodic re-evaluation of antibody levels, few firm recommendations are found in the leading guidelines.
Collapse
Affiliation(s)
- G Mena
- a Department of Preventive Medicine & Care Quality ; Hospital General Universitario de Castellón ; Castellón de la Plana , Spain
| | - A L García-Basteiro
- b ISGlobal; Barcelona Ctr. Int. Health Res. (CRESIB); Hospital Clínic - Universitat de Barcelona ; Barcelona , Spain.,c Centro de Investigação em Saúde deg Manhiça (CISM) ; Manhiça, Maputo , Mozambique
| | - J M Bayas
- b ISGlobal; Barcelona Ctr. Int. Health Res. (CRESIB); Hospital Clínic - Universitat de Barcelona ; Barcelona , Spain.,d Department of Preventive Medicine & Epidemiology ; Hospital Clínic de Barcelona; Universitat de Barcelona ; Barcelona , Spain
| |
Collapse
|
|
14
|
Sun HY, Sheng WH, Tsai MS, Lee KY, Chang SY, Hung CC. Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review. World J Gastroenterol 2014; 20:14598-14614. [PMID: 25356024 PMCID: PMC4209527 DOI: 10.3748/wjg.v20.i40.14598] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2013] [Revised: 12/24/2013] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients.
Collapse
|
|
15
|
Okwen MP, Reid S, Njei B, Mbuagbaw L. Hepatitis B vaccination for reducing morbidity and mortality in persons with HIV infection. Cochrane Database Syst Rev 2014; 10:CD009886. [PMID: 25300375 PMCID: PMC4830339 DOI: 10.1002/14651858.cd009886.pub2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatitis B vaccine has been recommended for use in people living with HIV (PLHIV) mostly because of the similarities in routes of infection and their prevalence in the same geographic areas. PLHIV may not develop sero-protection after receiving standard hepatitis B vaccine due to their compromised immune status. OBJECTIVES To evaluate the efficacy of hepatitis B virus vaccine in PLHIV compared to placebo or no vaccine. SEARCH METHODS We searched 6 English language databases in July 2012, and updated the search in June 2013 and August 2014. We searched the grey literature, conference proceedings, specialised web sites, and contacted experts in the field. SELECTION CRITERIA Randomised controlled trials of hepatitis B vaccine compared to placebo or no vaccine, evaluating relevant outcomes of efficacy and safety. DATA COLLECTION AND ANALYSIS Two review authors independently sought and extracted data on study design, participants, hepatitis B infection, hepatitis B related morbidity and mortality, anti-HBs immunogenicity and adverse effects related to vaccines from published articles or through correspondence with authors. Data were analysed qualitatively. MAIN RESULTS One double-blind randomised controlled trial with 26 participants who were on antiretroviral therapy (ART), comparing hepatitis B vaccine to placebo conducted in Spain met our eligibility criteria and was included in this review. The study ran for three years and participants were followed up on a monthly basis. The study reported adequate humoral response to vaccine at 12 months and no local or systematic side effects in both intervention and control groups. This humoral response was lost when the participants stopped taking ART. The sample size of the study was small and the study was conducted in a high income setting unlike the areas of highest burden of hepatitis B and HIV co-infections. AUTHORS' CONCLUSIONS The evidence from this study is insufficient to support any recommendations regarding the use of hepatitis B vaccine in PLHIV. Neither does this evidence demonstrate that hepatitis B vaccine is unsafe in PLHIV. Further randomised controlled trials in high prevalence areas are required to generate evidence on the long term efficacy and safety of hepatitis B vaccine in PLHIV with and without ART. Different regimens and routes of administration should also be explored.
Collapse
Affiliation(s)
- Mbah P Okwen
- Centre for the Development of Best Practices in Health (CDBPH), Yaoundé Central Hospital, Yaoundé, Cameroon
| | - Savanna Reid
- Department of Epidemiology and Biostatistics, University of Nevada, Las Vegas, Henderson, Nevada, USA
| | - Basile Njei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Lawrence Mbuagbaw
- Centre for the Development of Best Practices in Health (CDBPH), Yaoundé Central Hospital, Yaoundé, Cameroon
| |
Collapse
|
|
16
|
Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1. THE LANCET. INFECTIOUS DISEASES 2013; 12:966-76. [PMID: 23174382 DOI: 10.1016/s1473-3099(12)70243-8] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
HIV and hepatitis B virus co-infection leads to substantially increased morbidity and mortality compared with either infection alone. Immunisation with hepatitis B virus vaccine is the most effective way to prevent the infection in people with HIV; however, these patients have decreased vaccine responses and a short duration of protection compared with immunocompetent individuals. Control of HIV replication with highly active antiretroviral therapy and increased CD4 cell counts are associated with improved immune responses to hepatitis B vaccination. New vaccination strategies, such as increased vaccine dose, use of the intradermal route, and addition of adjuvants, could improve response rates in adults with HIV.
Collapse
|
|
17
|
Sayad B, Alavian SM, Najafi F, Soltani B, Shirvani M, Janbakhsh A, Mansouri F, Afsharian M, Vaziri S, Alikhani A, Bashiri H. Effects of Oral Levamisole as an Adjuvant to Hepatitis B Vaccine in HIV/ AIDS Patients: A Randomized Controlled Trial. HEPATITIS MONTHLY 2012; 12:e6234. [PMID: 23087761 PMCID: PMC3475133 DOI: 10.5812/hepatmon.6234] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2012] [Revised: 06/13/2012] [Accepted: 07/04/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Human immunodeficiency virus (HIV) infected patients are also frequently exposed to the hepatitis B virus (HBV), due to the common routes of transmission, therefore, prevention of hepatitis B results in decreased complications of the disease. OBJECTIVES Since the immune response of HIV patients to hepatitis B vaccination is less robust than that found in healthy individuals, this study aimed to evaluate the effect of a levamisole adjuvant on increasing the immune response. PATIENTS AND METHODS In this study, 89 HIV infected patients, without a history of HBV infection or vaccination, were randomly allocated into experimental (44 patients) and control (45 patients) groups. HBV vaccination was performed using the Hepavax-Gene TF vaccine, 40 μg three times at intervals of; zero, one, and three months. Levamisole 50 mg twice a day or a placebo, was administered to the experimental and control groups, respectively, for a period of six days before to six days after the vaccination. Immune response was evaluated by measuring hepatitis B surface antibodies (HBsAb) concurrently with the second and third vaccine administration, and at one and three months at the conclusion of the vaccination program. RESULTS The immune response following the threevaccinations was higher in those who were receiving levamisole compared with the controls (90% vs. 65.38%) (P = 0.05). Furthermore, the immune response and the mean antibody titer following the repeated vaccination in the experimental group showed a higher increase than in the control group. The immune response and the mean titer of antibody were not associated with; age, sex, body mass index, history of smoking and/or intravenous drug use in either of the groups. However, regarding CD4+ cells more than 200 cell/mm3, mean antibody production significantly increased in both groups. CONCLUSIONS Using levamisole with the hepatitis B vaccination can increase the immune response and antibody titer mean in HIV infected patients. Since these patients have a more complete response with CD4+ cells more than 200 cell/mm3, vaccination and effective adjuvants seem to be most beneficial when CD4+ cells are greater than 200 cell/mm3, in HIV infected patients.
Collapse
Affiliation(s)
- Babak Sayad
- Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
- Corresponding author: Babak Sayad, Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran. Tel.: +98-8317257708, Fax: +98-8318377734, E-mail:
| | - Seyyed Moayed Alavian
- Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Farid Najafi
- Health Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Bita Soltani
- Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Maria Shirvani
- Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Alireza Janbakhsh
- Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Feyzollah Mansouri
- Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Mandana Afsharian
- Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Siavash Vaziri
- Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Arash Alikhani
- Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Homayoon Bashiri
- Liver Disease and Hepatitis Research Center, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| |
Collapse
|
|
18
|
Phung BC, Launay O. Vaccination against viral hepatitis of HIV-1 infected patients. Hum Vaccin Immunother 2012; 8:554-9. [PMID: 22634451 DOI: 10.4161/hv.19105] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Reciprocal interactions between HIV and HAV or HBV can increase risk of morbidity and mortality in HIV disease and/or worsened the natural course of the hepatitis viruses. Hepatitis A vaccination is recommended for HIV infected patients at risk for exposure or severe disease: men who have sex with men, injecting drug users, patients with chronic liver disease and patients traveling in high endemic countries. As for healthy adults the scheme of vaccination is two doses 6 or 12 mo apart, nevertheless, seroconversion rates are lower. A third dose could improve the seroconversion rates. Hepatitis B vaccination is recommended for all HIV infected persons lacking prior immunity. As the immune response to hepatitis B vaccines is impaired in HIV-infected adults, four double doses of hepatitis B vaccine could enhance serological response. To assume a higher immune response, vaccines should be administered in HIV-infected patients with undetectable HIV viral load and high CD4 cell count.
Collapse
Affiliation(s)
- Bao-Chau Phung
- Université Paris Descartes, Faculté de Médicine, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, CIC de Vaccinologie Cochin Pasteur, Inserm, CIC BT505, Paris, France
| | | |
Collapse
|
|
19
|
Mena G, Llupià A, García-Basteiro AL, Díez C, León A, García F, Bayas JM. Assessing the immunological response to hepatitis B vaccination in HIV-infected patients in clinical practice. Vaccine 2012; 30:3703-9. [DOI: 10.1016/j.vaccine.2012.03.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2011] [Revised: 02/13/2012] [Accepted: 03/08/2012] [Indexed: 01/05/2023]
|
|
20
|
Powis JE, Raboud J, Ostrowski M, Loutfy MR, Kovacs C, Walmsley SL. The recombinant hepatitis B surface antigen vaccine in persons with HIV: is seroconversion sufficient for long-term protection? J Infect Dis 2012; 205:1534-8. [PMID: 22448009 DOI: 10.1093/infdis/jis243] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
A cohort of human immunodeficiency virus (HIV)-infected individuals with documented vaccine-induced hepatitis B surface antibody (HBsAb) seroconversion was evaluated retrospectively to determine factors associated with loss of protective levels of HBsAb. After a median follow-up of 43 months, 111 of the 152 participants (73%) maintained protective levels of HBsAb. HIV RNA suppression at vaccination was associated with persistence of protective levels of HBsAb (odds ratio, 3.83; P < .01). Booster doses were provided for those with loss of protective antibody levels, and hepatitis B virus-specific immune memory, as evaluated with T-cell proliferation assays, was poor despite the observation that boosters successfully reinduced protective levels of HBsAb.
Collapse
Affiliation(s)
- Jeff E Powis
- Department of Medicine, University of Toronto, Ontario, Canada.
| | | | | | | | | | | |
Collapse
|
|
21
|
Overton ET, Sungkanuparph S, Klebert M, Royal M, Demarco-Shaw D, Powderly WG, Aberg JA. GM-CSF Fails to Improve Immune Responses to Booster Hepatitis B Vaccination in HIV-Infected Individuals. Open Virol J 2011; 5:109-13. [PMID: 22043256 PMCID: PMC3201215 DOI: 10.2174/1874357901105010109] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2011] [Revised: 07/22/2011] [Accepted: 08/01/2011] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Hepatitis B (HBV) vaccination is an important preventive intervention for HIV-infected population. Data regarding booster HBV vaccine for persons with low HBV surface antibody (sAb) titers after vaccination in this immunocompromised population is lacking. METHODS We randomized 60 HIV-infected subjects lacking HBV protection after completion of 3 doses of HBV vaccine to receive a booster dose of HBV vaccine with 250mcg GM-CSF as an adjuvant or booster vaccine alone. RESULTS GM-CSF was safe with expected side effects. However, only 35% of persons receiving GM-CSF developed protective sAb while 50% in vaccine only arm developed protection (P = 0.47). Overall, only 28% of subjects maintained protective sAb 1 year after vaccination. CONCLUSIONS GM-CSF failed to improve responses to the booster HBV vaccination. Overall, response was poor with only 42% of persons responding at one month post-vaccination confirming booster vaccination with the current HBV vaccine has poor immunogenicity among HIV-infected persons. Further research is needed to develop optimal vaccination strategies in HIV-infected persons.
Collapse
|
|
22
|
Page AV, Liles WC. Colony-stimulating factors in the prevention and management of infectious diseases. Infect Dis Clin North Am 2011; 25:803-17. [PMID: 22054757 DOI: 10.1016/j.idc.2011.07.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Colony-stimulating factors (CSFs) are attractive adjunctive anti-infective therapies. Used to enhance innate host defenses against microbial pathogens, the myeloid CSFs increase absolute numbers of circulating innate immune effector cells by accelerating bone marrow production and maturation, or augment the function of those cells through diverse effects on chemotaxis, phagocytosis, and microbicidal functions. This article summarizes the evidence supporting the accepted clinical uses of the myeloid CSFs in patients with congenital or chemotherapy-induced neutropenia, and presents an overview of proposed and emerging uses of the CSFs for the prevention and treatment of infectious diseases in other immunosuppressed and immunocompetent patient populations.
Collapse
Affiliation(s)
- Andrea V Page
- Division of Infectious Diseases, Department of Medicine and SA Rotman Laboratories, McLaughlin-Rotman Centre for Global Health, Toronto General Hospital, University Health Network, University of Toronto, 13 Eaton North, Room 208, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | | |
Collapse
|
|
23
|
Abstract
Vaccination, the revolutionary prophylactic immunotherapy developed in the eighteenth century, has become the most successful and cost-effective of medical remedies available to modern society. Due to the remarkable accomplishments of the past century, the number of diseases and pathogens for which a traditional vaccine approach might reasonably be employed has dwindled to unprecedented levels. While this happy scenario bodes well for the future of public health, modern immunologists and vaccinologists face significant challenges if we are to address the scourge of recalcitrant pathogens like HIV and HCV and well as the significant obstacles to immunotherapy imposed by neoplastic self. Here, the authors review the clinical and preclinical literature to highlight the manner by which the host immune system can be successfully manipulated by cytokine adjuvants, thereby significantly enhancing the efficacy of a wide variety of vaccination platforms.
Collapse
|
|
24
|
Anthony DD, Umbleja T, Aberg JA, Kang M, Medvik K, Lederman MM, Peters MG, Koziel MJ, Overton ET. Lower peripheral blood CD14+ monocyte frequency and higher CD34+ progenitor cell frequency are associated with HBV vaccine induced response in HIV infected individuals. Vaccine 2011; 29:3558-63. [PMID: 21397720 DOI: 10.1016/j.vaccine.2011.02.092] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Revised: 02/24/2011] [Accepted: 02/25/2011] [Indexed: 01/26/2023]
Abstract
We evaluated immunologic predictors of response to HBV vaccine administered in the presence or absence of GM-CSF in HIV infected individuals. We measured peripheral blood hematopoietic progenitor, monocyte and myeloid-derived suppressor cell (MDSC) frequencies, and expression of GMCSF receptor on monocytes and MDSCs, at baseline and 4weeks after immunization in relation to antibody response. We observed higher baseline progenitor and lower monocyte frequencies among week 16 antibody responders. Week 4 decline in MDSC frequency was associated with week 16 antibody response, while administration of GM-CSF was associated with preservation of these cells. No significant differences in GM-CSF receptor expression were observed in the presence vs. absence of GM-CSF. These findings are consistent with a positive role of progenitor cells and a potential negative role of monocytes in vaccine response. Additionally, GM-CSF augmented the preservation of peripheral blood MDSC, which may contribute to the lack of improved vaccine responses.
Collapse
Affiliation(s)
- D D Anthony
- Case Western Reserve University, Cleveland, OH 44106, USA.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
|