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Ramrakhiani H, Le MH, Kam L, Nguyen B, Yeo YH, Levesley CR, Gudapati S, Barnett S, Cheung R, Nguyen MH. Long-Term Immunity and Anamnestic Response Following Hepatitis B Vaccination: A Systematic Review and Meta-Analysis. J Viral Hepat 2025; 32:e70003. [PMID: 39831733 DOI: 10.1111/jvh.70003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 01/01/2025] [Accepted: 01/10/2025] [Indexed: 01/22/2025]
Abstract
Using a systematic review and meta-analytic approach, this study determined the durability of HBV immunity and the prevalence of anamnestic response to a booster HBV vaccine dose in individuals previously vaccinated with a 3-dose HBV vaccine series as children or adolescents. Two researchers independently searched PubMed, Embase and Cochrane from inception to 6/1/2023 and performed data extraction. Studies that included individuals with significant comorbidities or < 5 years of follow-up were excluded. Of 2517 potential studies, we analysed 91 eligible studies (193,359 individuals from 208 cohorts [some studies provided data for more than one cohort]). Median age at vaccination was 0 years (range: 0-20.00). After a median follow-up of 10.15 years (range: 5-35), 63.2% (95% CI: 59.3-67.0) retained HBV immunity. HBV immunity declined by 6.62% per follow-up year (Ptrend < 0.0001). In meta-regression adjusting for vaccine type, follow-up time and geographic location, age at vaccination was significantly associated with retaining HBV immunity (adjusted odds ratio [aOR] 1.12 per year, p < 0.0001). Anamnestic response rate (44 studies, 66 cohorts, 29,040 patients) was 90.34% (95% CI: 86.84-92.98), with highest rates in Europe and Asia, but only study setting (clinical versus community-based: aOR 2.21, p = 0.034) was an independent factor. HBV immunity prevalence was about 60% after 10 years following childhood vaccination. Anamnestic response rate was about 90% and varied by study setting. Testing for immunity should be considered in individuals with high exposure risk and distant vaccination history with booster as needed.
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Affiliation(s)
- Hannah Ramrakhiani
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Brown University, Providence, Rhode Island, USA
| | - Michael H Le
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA
| | - Leslie Kam
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Brian Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Loma Linda School of Medicine, Loma Linda, California, USA
| | - Yee Hui Yeo
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Charles R Levesley
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Stanford University, Palo Alto, California, USA
| | - Surya Gudapati
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Scott Barnett
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Division of Gastroenterology and Hepatology, Palo Alto Veterans Affairs Medical Center, Palo Alto, California, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California, USA
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Sperle I, Lassen SG, Schlaud M, Dörre A, Dudareva S, Poethko-Müller C, Harder T. Prevalence of vaccine-derived hepatitis B surface antibodies in children and adolescents in Germany: results from a population-based survey, 2014-2017. BMC Infect Dis 2024; 24:318. [PMID: 38491438 PMCID: PMC10941582 DOI: 10.1186/s12879-024-09201-7] [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: 08/22/2023] [Accepted: 03/06/2024] [Indexed: 03/18/2024] Open
Abstract
INTRODUCTION Childhood vaccination against hepatitis B has been recommended in Germany since 1995. WHO defines a primary vaccination series as successful if the initial hepatitis B surface antibody (anti-HBs) level is ≥ 10 IU/L directly after vaccination. Anti-HBs levels vary depending on the number of doses, type of vaccine, and time interval between the last two doses. In 2021, Germany began to recommend three instead of four doses of polyvalent hepatitis-B-containing vaccines. Our aim was to estimate the proportion of vaccinated children in Germany with anti-HBs levels < 10 IU/L, 10-99 IU/L, and ≥ 100 IU/L by number and type of vaccine, and assess if number of doses and compliance with recommended time interval between the last two doses are associated with an anti-HBs level ≥ 10 IU/L when considering type of vaccine and time since last dose. METHODS We used data from a national cross-sectional study (2014-2017) of children (3-17 years). We excluded participants with unknown vaccination dates, unreadable or incomplete vaccination cards, and hepatitis B virus (HBV)-positive participants. We defined a recommended schedule as a vaccination series with at least six months between the two last doses and having three doses or more. We calculated weighted anti-HBs sero-prevalence for three anti-HBs levels: < 10 IU/L, 10-99 IU/L and ≥ 100 IU/L. We fitted two logistic regression models to examine the relationship between number of doses and recommended schedule on anti-HBs levels (≥ 10 IU/L and ≥ 100 IU/L) considering time since last dose and type of vaccine (Infanrix, Hexavac, Monovalent). RESULTS We included 2,489 participants. The weighted proportion of vaccinated children per anti-HBs level was < 10 IU/L: 36.3% [95%CI 34.0-38.7%], 10-99 IU/L: 35.7% [33.2-38.2%] and ≥ 100 IU/L: 28.0% [25.9-30.2%]. We did not find an association between a recommended schedule of three versus four doses and anti-HBs ≥ 10 IU/L or ≥ 100 IU/L. CONCLUSIONS Anti-HBs levels in later childhood were about equal, whether children received three or four doses. This implies that the change in the recommendations does not affect the anti-HBs level among children in Germany. Future studies are needed on the association of anti-HBs levels and adequate sustained protection against HBV.
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Affiliation(s)
- Ida Sperle
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
- Postgraduate Training for Applied Epidemiology (PAE), Robert Koch Institute, Berlin, Germany.
- ECDC Fellowship Programme, Field Epidemiology Path (EPIET), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.
| | - Sofie Gillesberg Lassen
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- PhD Programme, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Martin Schlaud
- Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany
| | - Achim Dörre
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Sandra Dudareva
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | | | - Thomas Harder
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
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Harris AM, Schillie S. Hepatitis B and Hepatitis D Viruses. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2023:1125-1133.e4. [DOI: 10.1016/b978-0-323-75608-2.00213-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Lack of relationship between 25-hydoxyvitamin D concentration and a titer of antibodies to hepatitis B surface antigen in children under 12 years of age. PLoS One 2022; 17:e0277473. [DOI: 10.1371/journal.pone.0277473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 10/27/2022] [Indexed: 11/12/2022] Open
Abstract
The effect of vitamin D levels on the response to the hepatitis B vaccine in childhood and the induced levels of antibodies against the hepatitis B surface antigen (anti-HBs) is not yet well understood. The study aimed to investigate the relationship between age, serum 25-hydroxyvitamin D (25(OH)D) concentration and anti-HBs titer among children under 12 years old. Serum 25(OH)D concentration and anti-HBs titer were determined in 352 healthy Caucasian children with the average age of 4.2 (2.5; 6.3) years. All children were vaccinated with 3 doses of hepatitis B vaccine (Engerix-B, GlaxoSmithKline Pharmaceuticals Limited) in infancy according to the Centers for Disease Control and Prevention recommendations. Only 14.5% of children had an optimal concentration of 25(OH)D ≥ 30 ng/mL and 71.9% children had a seroprotective anti-HBs titer ≥ 10 mIU/mL. Significant negative correlations were found between 25(OH)D, anti-HBs titer and age (r = –0.420, p = 0.000; r = –0.425, p = 0.000, respectively), and a weak positive correlation between 25(OH)D concentration and anti-HBs titer (r = 0.243, p = 0.000). Analysis of six clusters of children demonstrated that age is the main factor affecting anti-HBs titer. One third of children under 12 years of age had nonprotective anti-HBs titer < 10 mIU/mL and around 40% had vitamin D deficiency. We conclude that vitamin D status has no impact on anti-HBs titer in children vaccinated against hepatitis B virus in infancy. Age, so time since the receipt of the last dose of hepatitis B vaccine, is the main factor influencing a decline in anti-HBs titer.
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Agallou M, Koutsoni OS, Michail M, Zisimopoulou P, Tsitsilonis OE, Karagouni E. Antibody and T-Cell Subsets Analysis Unveils an Immune Profile Heterogeneity Mediating Long-term Responses in Individuals Vaccinated Against SARS-CoV-2. J Infect Dis 2022; 227:353-363. [PMID: 36259394 PMCID: PMC9620767 DOI: 10.1093/infdis/jiac421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 10/14/2022] [Accepted: 10/18/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Based on the fact that coronavirus disease 2019 (COVID-19) is still spreading despite worldwide vaccine administration, there is an imperative need to understand the underlying mechanisms of vaccine-induced interindividual immune response variations. METHODS We compared humoral and cellular immune responses in 127 individuals vaccinated with either BNT162b2, mRNA-1273, or ChAdOx1-nCoV-19 vaccine. RESULTS Both mRNA vaccines induced faster and stronger humoral responses as assessed by high spike- and RBD-specific antibody titers and neutralizing efficacy in comparison to ChAdOx1-nCoV-19 vaccine. At 7 months postvaccination, a decreasing trend in humoral responses was observed, irrespective of the vaccine administered. Correlation analysis between anti-S1 IgG and interferon- (IFN-) production unveiled a heterogeneous immune profile among BNT162b2-vaccinated individuals. Specifically, vaccination in the high-responder group induced sizable populations of polyfunctional memory CD4 helper T cells (TH1), follicular helper T cells (TFH), and T cells with features of stemness (TSCM), along with high neutralizing antibody production that persisted up to 7 months. In contrast, low responders were characterized by significantly lower antibody titers and memory T cells and a considerably lower capacity for interleukin-2 and IFN- production. CONCLUSIONS We identified that long-term humoral responses correlate with the individuals ability to produce antigen-specific persistent memory T-cell populations.
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Affiliation(s)
- Maria Agallou
- Immunology of Infection Laboratory, Hellenic Pasteur Institute, Athens, Greece
| | - Olga S Koutsoni
- Laboratory of Cellular Immunology, Hellenic Pasteur Institute, Athens, Greece
| | - Maria Michail
- Laboratory of Molecular Neurobiology and Immunology, Hellenic Pasteur Institute, Athens, Greece,Department of Biology, National and Kapodistrian University of Athens, Athens, Greece
| | - Paraskevi Zisimopoulou
- Laboratory of Molecular Neurobiology and Immunology, Hellenic Pasteur Institute, Athens, Greece
| | - Ourania E Tsitsilonis
- Department of Biology, National and Kapodistrian University of Athens, Athens, Greece
| | - Evdokia Karagouni
- Correspondence: Evdokia Karagouni, PhD, Hellenic Pasteur Institute, 127 Vas. Sofias Ave, 115 21 Athens, Greece ()
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Romano’ L, Zanetti AR. Hepatitis B Vaccination: A Historical Overview with a Focus on the Italian Achievements. Viruses 2022; 14:1515. [PMID: 35891495 PMCID: PMC9320049 DOI: 10.3390/v14071515] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/08/2022] [Accepted: 07/08/2022] [Indexed: 11/16/2022] Open
Abstract
Vaccination is the most effective way to control and prevent acute and chronic hepatitis B, including cirrhosis and HCC, on a global scale. According to WHO recommendations, 190 countries in the world have introduced hepatitis B vaccination into their national childhood immunization programs with an excellent profile of safety, immunogenicity, and effectiveness. Following vaccination, seroprotection rates are close to 100% in healthy children and over 95% in healthy adults. Persistence of anti-HBs is related to the antibody peak achieved after vaccination. The peak is higher the longer the antibody duration is. Loss of anti-HBs does not necessarily mean loss of immunity since most vaccinated individuals retain immune memory for HBsAg and rapidly develop strong anamnestic responses when boosted. Evidence indicates that the duration of protection can persist for at least 35 years after priming. Hence, booster doses of vaccines are currently not recommended to sustain long-term immunity in healthy vaccinated individuals. In Italy, vaccination against hepatitis B is met with success. In 2020, Italy became one of the first countries in Europe to be validated for achieving the WHO regional hepatitis B control targets.
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Affiliation(s)
- Luisa Romano’
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi, 20133 Milano, Italy;
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Gomes LC, Sanson MCG, Brainin P, de Melo MDCV, de Souza RM, Mazaro J, Lima KO, Resende JS, Vieira IVM, Mesquita EDS, Matos LO, Dutra ICS, Palmisano G, Wrenger C, Marinho CRF, da Silva RDSU. Levels of hepatitis B antibody titers are affected by age and doses gap time in children from a high endemic area of the western Amazon. PLoS One 2021; 16:e0253752. [PMID: 34197516 PMCID: PMC8248698 DOI: 10.1371/journal.pone.0253752] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 06/14/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Despite completion of the vaccine schedule for hepatitis B virus (HBV), children may display levels of HBV surface antibodies (anti-HBs) that are considered inadequate for sufficient protection (<10 IU/L). AIMS Our aim was to investigate if age and gap time between HBV vaccine doses may negatively affect the levels of anti-HBs in children, and if these relationships are modified by sex. METHODS In a high-endemic HBV region of the western Brazilian Amazon we enrolled children who had completed the HBV vaccine schedule. All children underwent analysis of anti-HBs and a clinical examination. RESULTS We included 522 children (mean age 4.3 ± 0.8 years; 50% male). Median anti-HBs was 28.4 [interquartile range (IQR) 5.4 to 128.6] IU/L and 32% had anti-HBs <10 IU/L. The median gap time from last to preceding dose was 2.4 [IQR 2.1 to 3.3] months. Levels of anti-HBs decreased with higher age (-42% per year increase [95%CI -56% to -24%], p<0.001), but not with longer gap time (+23% per month increase [95%CI -16% to +62%], p = 0.249). After adjusting for relevant confounders, gap time became significant (p = 0.032) and age remained a significant predictor of anti-HBs (p<0.001). CONCLUSION One third of assessed children displayed anti-HBs <10 IU/L. Levels of anti-HBs decreased with higher age and increased with longer gap time between the last two doses.
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Affiliation(s)
- Laura Cordeiro Gomes
- Health and Sport Science Center, Federal University of Acre, Rio Branco, Acre, Brazil
| | | | | | | | | | | | - Karine Oliveira Lima
- Multidisciplinary Center, Federal University of Acre, Cruzeiro do Sul, Acre, Brazil
| | - Júnia Silva Resende
- Multidisciplinary Center, Federal University of Acre, Cruzeiro do Sul, Acre, Brazil
| | | | | | - Luan Oliveira Matos
- Multidisciplinary Center, Federal University of Acre, Cruzeiro do Sul, Acre, Brazil
| | | | - Giuseppe Palmisano
- Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Carsten Wrenger
- Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
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The positive rates of hepatitis B surface antibody in youths after booster vaccination: a 4-year follow-up study with large sample. Biosci Rep 2021; 41:229067. [PMID: 34151935 PMCID: PMC8415346 DOI: 10.1042/bsr20210182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is still a public issue of the world. Hepatitis B vaccination is widely used as an effective measure to prevent HBV infection. This large-sample study aimed to evaluate the positive rates of hepatitis B surface antibody (anti-HBs) in youths after booster vaccination. METHODS A total of 37,788 participants were divided into two groups according to the baseline levels of anti-HBs before booster vaccination: the negative group (anti-HBs (-)); the positive group (anti-HBs (+)). Participants were tested for anti-HBs levels after receiving a booster vaccine 1 year and 4 years. RESULTS The positive rates of anti-HBs were 34.50%, 73.8% and 67.32% before booster vaccination at 1 year and 4 years after vaccination, respectively. At four years after the booster vaccination, the positive rates of 13 to 18 years were 47.54%, which was the lowest level among all youths age groups. In the anti-HBs (-) group, the positive conversion rates of anti-HBs were 74.62% at 1 year after receiving a booster vaccine, and 67.66% at 4 years after vaccination. In the anti-HBs (+) group, the positive maintenance rates of anti-HBs were 70.16% after 1 year, and 66.66% after 4 years. Compared with the baseline anti-HBs (+) group, the positive rates of the baseline anti-HBs (-) group were higher at 1 year and 4 years after receiving the booster vaccine. CONCLUSIONS The positive rates of anti-HBs declined over time, especially the positive maintenance rates were the lowest at age of 13 to 18 years.
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Porcine Circovirus 2 Genotypes, Immunity and Vaccines: Multiple Genotypes but One Single Serotype. Pathogens 2020; 9:pathogens9121049. [PMID: 33327478 PMCID: PMC7764931 DOI: 10.3390/pathogens9121049] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 12/08/2020] [Accepted: 12/12/2020] [Indexed: 02/06/2023] Open
Abstract
Identified for the first time in the 1990s, Porcine circovirus 2 (PCV-2) should not be considered an emerging virus anymore. Nevertheless, many aspects of its biology and epidemiology are still controversial. Particularly, its high evolutionary rate has caused the emergence of several variants and genotypes, alternating on the worldwide proscenium. The biological and practical implications of such heterogenicity are unfortunately largely unknown. The effectiveness of currently available vaccines against new genotypes that have emerged over time has been the topic of an intense debate and often inconclusive or contradictory results between experimental, field, and epidemiological studies have been gathered. The challenge in establishing an effective PCV-2 disease model, the peculiarities in experimental design and settings and the strains involved could justify the observed differences. The present work aims to summarize and critically review the available knowledge on PCV-2 genetic heterogeneity, immunity, and vaccine efficacy, organizing and harmonizing the available data from different sources, shedding light on this complex field and highlighting current knowledge gaps and future perspectives. So far, all vaccines in the market have shown great efficacy in reducing clinical signs associated to diseases caused by PCV-2, independently of the genotype present in the farm. Moreover, experimental data demonstrated the cross-protection of PCV-2a vaccines against the most widespread genotypes (PCV-2a, PCV-2b, and PCV-2d). Therefore, despite the significant number of genotypes described/proposed (PCV-2a to PCV-2i), it seems one single PCV-2 serotype would exist so far.
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Verso MG, Costantino C, Marrella A, Immordino P, Vitale F, Amodio E. Kinetics of Anti-Hepatitis B Surface Antigen Titers in Nurse Students after a Two-Year Follow-Up. Vaccines (Basel) 2020; 8:E467. [PMID: 32839391 PMCID: PMC7563960 DOI: 10.3390/vaccines8030467] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 08/14/2020] [Accepted: 08/18/2020] [Indexed: 12/14/2022] Open
Abstract
Infection caused by hepatitis B virus (HBV) can be prevented through a safe and effective vaccine. This study analysed the kinetics of serum antibodies against hepatitis B surface antigen (HBsAg) (anti-HBs) titers in relation to previous vaccine boosters in Italian nursing students who were followed up for two years. Serum anti-HBs titers were evaluated at the first visit, after vaccine booster (if required) and at visit after two years. Overall, 483 students (mean age = 21.7 years; SD = 3.7) with median anti-HBs IgG titer of 6 mUI/mL (interquartile range (IQR) = 0-34) were enrolled. A total of 254 (52.5%) students with a titer lower than 10 mIU/mL were offered an anti-HBV booster at the first visit. Among these students, an exponential relation between anti-HBs IgG titer, one month after HBV booster and anti-HBs IgG titer two years later was found (y = 3.32 exp (0.0045x); R2 = 0.48; p < 0.001). Students with anti-HBV titer higher than 10 mIU/mL (N = 229) were followed up, and anti-HBs IgG titers at follow-up visit linearly correlated with anti-HBV baseline titers (y = 0.86x + 26.2; R2 = 0.67; p < 0.001). A decrease in anti-HBs titers can be expected a few years after the anti-HBV booster dose. This reduction is more pronounced than that observed in students not administered the booster dose and is exponential with respect to basal titers assessed after the booster dose.
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Affiliation(s)
- Maria Gabriella Verso
- Occupational Health Unit, Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties “G. D’Alessandro”, University of Palermo, 90133 Palermo, Italy
| | - Claudio Costantino
- Section of Hygiene, Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties “G. D’Alessandro”, University of Palermo, 90133 Palermo, Italy; (C.C.); (A.M.); (P.I.); (F.V.); (E.A.)
| | - Alessandro Marrella
- Section of Hygiene, Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties “G. D’Alessandro”, University of Palermo, 90133 Palermo, Italy; (C.C.); (A.M.); (P.I.); (F.V.); (E.A.)
| | - Palmira Immordino
- Section of Hygiene, Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties “G. D’Alessandro”, University of Palermo, 90133 Palermo, Italy; (C.C.); (A.M.); (P.I.); (F.V.); (E.A.)
| | - Francesco Vitale
- Section of Hygiene, Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties “G. D’Alessandro”, University of Palermo, 90133 Palermo, Italy; (C.C.); (A.M.); (P.I.); (F.V.); (E.A.)
| | - Emanuele Amodio
- Section of Hygiene, Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties “G. D’Alessandro”, University of Palermo, 90133 Palermo, Italy; (C.C.); (A.M.); (P.I.); (F.V.); (E.A.)
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Evaluation of hepatitis B, hepatitis A, measles, rubella, mumps and varicella antibody seroprevalences in Vocational School of Health Students. JOURNAL OF CONTEMPORARY MEDICINE 2020. [DOI: 10.16899/jcm.718639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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No evidence of occult HBV infection in population born after mass vaccination. Wien Med Wochenschr 2020; 170:218-223. [PMID: 32274600 DOI: 10.1007/s10354-020-00748-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Accepted: 03/16/2020] [Indexed: 12/13/2022]
Abstract
Despite access to efficient hepatitis B virus (HBV) vaccine and universal immunization schedules, HBV infection remains a global health concern. HBV infection has decreased by this program. Nevertheless, breakthrough infections occur due to generation of occult HBV infection (OBI) and surface gene mutants in the immunized population. We aimed to determine the presence of OBI in a population born after initiation of nationwide HBV vaccination in Tehran, Iran. A HBV mass vaccination schedule was launched in Iran in 1993. For this study, we enrolled 1120 cases younger than 24 years. ELISA was applied to evaluate the presence of HBsAg, anti-HBs and anti-HBc. HBV-DNA presence was determined in all HBsAg-negative cases using nested polymerase chain reaction. The prevalence of HBsAg, anti-HBc and anti-HBs was 0.1, 0.54 and 39.9% respectively. Out of 6 anti-HBc-positive individuals, 4 cases also had anti-HBs. One case revealed HBsAg co-existence and the other one showed isolated anti-HBc. HBV-DNA was not detected in HBsAg-negative specimens. A very low prevalence of HBsAg and isolated anti-HBc was observed and no occult HBV infection was detected. It seems that evasion mutants are not a potential threat for HBV universal immunization efficacy in the vaccinated population.
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Vesikari T, Xu J, Johnson DR, Hall J, Marček T, Goveia MG, Acosta CJ, Lee AWT. Hepatitis B and pertussis antibodies in 4- to 5-year-old children previously vaccinated with different hexavalent vaccines. Hum Vaccin Immunother 2020; 16:867-874. [PMID: 31689166 PMCID: PMC7227712 DOI: 10.1080/21645515.2019.1673119] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 09/05/2019] [Accepted: 09/21/2019] [Indexed: 12/17/2022] Open
Abstract
In randomized active-comparator controlled studies, DTaP5-HB-IPV-Hib showed comparable immunogenicity and safety to other licensed vaccines. This study assessed persistence of anti-hepatitis B surface antigen (HBs) and anti-pertussis antibodies, when children were 4 to 5 years of age, 3 to 4 years after initial infant/toddler hexavalent vaccination. This was an extension of 2 European studies in which infants/toddlers received either DTaP5-HB-IPV-Hib or DTaP3-HB-IPV/Hib on a 2 + 1 or 3 + 1 schedule. Primary endpoints included percentages with anti-HBs ≥10 mIU/mL, and anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), anti-pertactin (PRN), and anti-fimbriae types 2 & 3 (FIM) greater than or equal to the lower limit of quantitation (LLOQ). One month after 2 + 1 or 3 + 1 dosing, nearly all toddlers had anti-HBs ≥10 mIU/mL, and responded to the received pertussis antigens. Approximately 3 to 4 years later, 65.8%-70.2% in the DTaP5-HB-IPV-Hib and 82.0%-83.7% in the DTaP3-HB-IPV/Hib groups, respectively, had anti-HBs ≥10 mIU/mL. Percentages of children with pertussis antibodies above LLOQ after 2 + 1 dosing were 58.4% and 41.5% (anti-PT), 80.9% and 88.3% (anti-FHA), 66.1% and 72.6% (anti-PRN), and 94.4% and 3.3% (anti-FIM), in the DTaP5-HB-IPV-Hib and DTaP3-HB-IPV/Hib groups, respectively. This study demonstrated, as expected, waning of hepatitis B and pertussis antibodies during the 3 to 4 years after completion of a 3 + 1 or 2 + 1 hexavalent vaccination schedule. Nonetheless, anti-HBs levels ≥10 IU/mL and detectable antibodies against acellular pertussis antigens persisted in most study participants. The implications of these findings for the long-term prevention of hepatitis B and pertussis are further discussed.
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Affiliation(s)
- Timo Vesikari
- Department of Pediatrics, University of Tampere, Tampere, Finland
| | - Jin Xu
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
| | | | - Jessie Hall
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
| | | | - Michelle G. Goveia
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
| | - Camilo J. Acosta
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
| | - Andrew Wen-Tseng Lee
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
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15
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Hess L, Riesenberg K, Rolston KVI, Nesher L. Administering an additional hepatitis B vaccination dose after 18 years maintains adequate long-term protection levels in healthcare workers. Infect Dis (Lond) 2020; 52:330-335. [PMID: 31983251 DOI: 10.1080/23744235.2020.1718201] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: HBV (hepatitis B virus) vaccination in first year of life is recommended to prevent infection. Observational studies have suggested that vaccination at birth provides protection for 90% of the population for 30 years. Data on response to booster doses and long-term protection are lacking.Methods: We compared HBV antibody levels of healthcare students who were immunized for HBV with a primary series during their first year of life (primary) to students who were immunized with a primary series and received an additional dose at age 18 (boosted) four years earlier. Antibody titres ≥10 mIU/mL were considered adequate. Those that were inadequate received another dose and were reassessed.Results: We assessed 381 students, 80.1% were primary and 19.9% boosted. A significantly higher percentage of students in the boosted group had antibody titre levels ≥10 mIU/mL compared to primary group (88.1% vs. 41.3%, p < .001). Of 179 students in the primary group with inadequate antibody levels, 134 received a booster dose and 126 of them (94%) developed anti-HBs levels ≥10 mIU/mL. Of 9 students with inadequate levels in the boosted group, 8 received another booster dose and all developed adequate levels.Conclusions: Primary vaccination against HBV at birth does not necessarily provide lifelong adequate antibody levels. Boosting at 18 years reinforces antibody levels for at least four more years. Current guidelines recommend testing and boosting all medical personal. Based on our study, it may be prudent to extend this practice to all individuals who are at higher risk.
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Affiliation(s)
- Liza Hess
- Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel
| | - Klaris Riesenberg
- Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.,Internal Medicine Division, Infectious Disease Institute, Soroka Medical Center, Beersheba, Israel
| | - Kenneth V I Rolston
- Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lior Nesher
- Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.,Internal Medicine Division, Infectious Disease Institute, Soroka Medical Center, Beersheba, Israel
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16
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Franzo G, Legnardi M, Tucciarone CM, Drigo M, Martini M, Cecchinato M. Evolution of infectious bronchitis virus in the field after homologous vaccination introduction. Vet Res 2019; 50:92. [PMID: 31706335 PMCID: PMC6842459 DOI: 10.1186/s13567-019-0713-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 09/25/2019] [Indexed: 11/10/2022] Open
Abstract
Despite the fact that vaccine resistance has been typically considered a rare phenomenon, some episodes of vaccine failure have been reported with increasing frequency in intensively-raised livestock. Infectious bronchitis virus (IBV) is a widespread avian coronavirus, whose control relies mainly on extensive vaccine administration. Unfortunately, the continuous emergence of new vaccine-immunity escaping variants prompts the development of new vaccines. In the present work, a molecular epidemiology study was performed to evaluate the potential role of homologous vaccination in driving IBV evolution. This was undertaken by assessing IBV viral RNA sequences from the ORF encoding the S1 portion of viral surface glycoprotein (S) before and after the introduction of a new live vaccine on broiler farms in northern-Italy. The results of several biostatistics analyses consistently demonstrate the presence of a higher pressure in the post-vaccination period. Natural selection was detected essentially on sites located on the protein surface, within or nearby domains involved in viral attachment or related functions. This evidence strongly supports the action of vaccine-induced immunity in conditioning viral evolution, potentially leading to the emergence of new vaccine-escape variants. The great plasticity of rapidly-evolving RNA-viruses in response to human intervention, which extends beyond the poultry industry, is demonstrated, claiming further attention due to their relevance for animal and especially human health.
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Affiliation(s)
- Giovanni Franzo
- Department of Animal Medicine, Production and Health (MAPS), University of Padua, Viale dell’Università 16, 35020 Legnaro, PD Italy
| | - Matteo Legnardi
- Department of Animal Medicine, Production and Health (MAPS), University of Padua, Viale dell’Università 16, 35020 Legnaro, PD Italy
| | - Claudia Maria Tucciarone
- Department of Animal Medicine, Production and Health (MAPS), University of Padua, Viale dell’Università 16, 35020 Legnaro, PD Italy
| | - Michele Drigo
- Department of Animal Medicine, Production and Health (MAPS), University of Padua, Viale dell’Università 16, 35020 Legnaro, PD Italy
| | - Marco Martini
- Department of Animal Medicine, Production and Health (MAPS), University of Padua, Viale dell’Università 16, 35020 Legnaro, PD Italy
| | - Mattia Cecchinato
- Department of Animal Medicine, Production and Health (MAPS), University of Padua, Viale dell’Università 16, 35020 Legnaro, PD Italy
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17
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Tfifha M, Kacem S, Ben Rejeb M, Naija S, Boujaafar N, Abroug S, Trabelsi A. Evaluation of antibody persistence after a four-dose primary hepatitis B vaccination and anamnestic immune response in children under 6 years. J Med Microbiol 2019; 68:1686-1693. [PMID: 31592765 DOI: 10.1099/jmm.0.001086] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Introduction. Tunisia is an intermediate hepatitis B virus (HBV) endemic country. The vaccination against hepatitis B was introduced in 1995 including four doses with a first dose administrated at birth. Decreasing the level of antibodies against hepatitis B surface antigen (anti-HBs) over time can be alarming. This study was conducted to explore the anti-HBV immune response among children under 6 years old, vaccinated according to the national vaccination schedule, by evaluating the immunological response to primary vaccination and by exploring the anamnestic immune response to a booster dose.Methods. We conducted a cross-sectional prospective study from June 2016 to June 2017 (n=180), based on voluntary participation. Children were recruited from the public pediatric ward sectors in Sahloul University Hospital of Sousse in Central Tunisia. An anti-HB titre was determined based on electro-chemiluminescence micro-particle immunoassay (ECLIA), using Elecsys Anti-HBs II kit, Roche.Results. Mean age at the time of enrollment in the study was 33±14.8 months. The seroprotection rate was 77.2 %. The anti-HB titre differed significantly between the different age groups (P=0.002). The predicting variable for having no seroprotective antibody level was older age. Children with anti-HB levels <10 IU l- 1 were offered an additional dose of HBV vaccine. Anamnestic response 1 month after the challenge dose was observed in 100 % of subjects. The probability of developing a high antibody response, following the booster dose increased in conjunction with an increased pre-booster antibody level.Conclusion. The response to a booster dose suggests the persistence of immune memory in almost all vaccinated individuals. Although a booster dose increases substantially anti-HB titre, the clinical relevance of such an increase remains unknown.
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Affiliation(s)
- Miniar Tfifha
- Pediatric department, Sahloul University Hospital, 4054 Sousse, Tunisia
| | - Saoussen Kacem
- LR14SP02, Epidemiology and Immunogenetics of Human Viral Infections, Laboratory of Microbiology, Sahloul University Hospital, 4054 Sousse, Tunisia.,Faculty of Pharmacy, University of Monastir, Monastir, Tunisia
| | - Mohamed Ben Rejeb
- Department of Prevention and Care Safety, Sahloul University Hospital, 4054 Sousse, Tunisia
| | - Said Naija
- LR14SP02, Epidemiology and Immunogenetics of Human Viral Infections, Laboratory of Microbiology, Sahloul University Hospital, 4054 Sousse, Tunisia
| | - Noureddine Boujaafar
- Laboratory of Microbiology, Sahloul University Hospital, 4054 Sousse, Tunisia.,Faculty of Pharmacy, University of Monastir, Monastir, Tunisia
| | - Saoussen Abroug
- Pediatric department, Sahloul University Hospital, 4054 Sousse, Tunisia
| | - Abdelhalim Trabelsi
- LR14SP02, Epidemiology and Immunogenetics of Human Viral Infections, Laboratory of Microbiology, Sahloul University Hospital, 4054 Sousse, Tunisia.,Faculty of Pharmacy, University of Monastir, Monastir, Tunisia
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18
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In pursuit of control and elimination: update on hepatitis A and B epidemiology and prevention strategies. Curr Opin Pediatr 2018; 30:689-697. [PMID: 30188873 DOI: 10.1097/mop.0000000000000672] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE OF REVIEW This review describes the impact of recommendations for routine immunization of infants and children against hepatitis A and hepatitis B, the changing epidemiology of these infections, and the remaining challenges to controlling or eliminating these diseases in the United States. RECENT FINDINGS Rates of hepatitis A and B have significantly declined because of childhood vaccination programs and long-term protection provided by infant immunization. However, hepatitis A immunization rates remain lower than other vaccines, and outbreaks continue to occur in part due to a growing number of susceptible adults. The Advisory Committee on Immunization Practice has updated pre and postexposure prophylaxis and travel recommendations for hepatitis A prevention in young infants, as well as recommendations to reduce ongoing perinatal transmission of hepatitis B. SUMMARY Pediatric healthcare providers should continue to immunize all infants against hepatitis A and B and ensure that no child outgrows the pediatric practice without being vaccinated. To address hepatitis A, providers should be aware of new recommendations for unimmunized travelers, use vaccines to prevent and control outbreaks, and ensure postexposure prophylaxis. Universal vaccination of infants against hepatitis B should begin before hospital discharge. The prevention of perinatal transmission is critical for control and possible eradication of hepatitis B.
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19
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Tang X, Allain JP, Wang H, Rong X, Chen J, Huang K, Xu R, Wang M, Huang J, Liao Q, Shan Z, Luo S, Li T, Li C, Fu Y. Incidence of hepatitis B virus infection in young Chinese blood donors born after mandatory implementation of neonatal hepatitis B vaccination nationwide. J Viral Hepat 2018; 25:1008-1016. [PMID: 29624818 DOI: 10.1111/jvh.12901] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 02/16/2018] [Indexed: 01/17/2023]
Abstract
This study was carried out to determine the incidence of hepatitis B virus (HBV) infection in the young generation born after mandatory implementation of hepatitis B vaccination since 1992. Repeat blood donors born between 1992 and 1997 were enrolled, who gave blood at least twice during the past 3 years. Donors were tested for HBV infection markers of HBsAg, anti-HBc, anti-HBs and viral DNA by immunoassays (EIAs) and nucleic acid tests (NAT). A total of 14 937 pre-donation screening qualified young repeat donors aged 18-23 years were tested with 9 (0.06%) being HBsAg by EIA and 10 (1:1494) HBV DNA positive by Ultrio NAT (10.4 IU/mL), respectively. HBV DNA was further detected in 1:192 (9/1732) anti-HBc+ repeat donors with Ultrio Plus NAT (3.4 IU/mL). Most cases were identified as occult HBV infection (OBI). Of 14 937 repeat donors, 20.9% were anti-HBc+ positive, while approximately 50% of 12 024 repeat donors were anti-HBs negative or had levels <100 IU/L. HBsAg+ or OBI strains were classified as wild type of genotype B or genotype C. Incident HBV infection in repeat donors was approximately 1:18.5 person-years (1.1%/year) but significantly less frequent in donors with confirmed HBV vaccination (2.4%-3.3%) than those unsure of vaccination status (10.5%; P = .0023). Hepatitis B virus vaccination appears largely protective of HBV infection, but incidence of infections increases in young adults with mostly undetectable or low anti-HBs or occasionally high anti-HBs. A boost of hepatitis B vaccine for adolescents prior to age 18 years may reduce HBV infection, and implementation of more sensitive NAT in blood donation screening may improve HBV safety in blood transfusion.
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Affiliation(s)
- X Tang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,Guangzhou Blood Center, Guangzhou, China
| | - J-P Allain
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,University of Cambridge, Cambridge, UK
| | - H Wang
- Guangzhou Blood Center, Guangzhou, China
| | - X Rong
- Guangzhou Blood Center, Guangzhou, China
| | - J Chen
- Guangzhou Blood Center, Guangzhou, China
| | - K Huang
- Guangzhou Blood Center, Guangzhou, China
| | - R Xu
- Guangzhou Blood Center, Guangzhou, China
| | - M Wang
- Guangzhou Blood Center, Guangzhou, China
| | - J Huang
- Guangzhou Blood Center, Guangzhou, China
| | - Q Liao
- Guangzhou Blood Center, Guangzhou, China
| | - Z Shan
- Guangzhou Blood Center, Guangzhou, China
| | - S Luo
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - T Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - C Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,School of Public Health, Southern Medical University, Guangzhou, China
| | - Y Fu
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,Guangzhou Blood Center, Guangzhou, China
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20
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Wu W, Lv J, Liu J, Yan B, Feng Y, Xu A, Zhang L. Persistence of immune memory among adults with normal and high antibody response to primary hepatitis B vaccination: Results from a five-year follow-up study in China. Hum Vaccin Immunother 2018; 14:2485-2490. [PMID: 29993330 DOI: 10.1080/21645515.2018.1477911] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
Abstract
Immune memory after hepatitis B vaccination among adults is still under investigation. In this study, adults who had normal and high antibody response to the primary series of hepatitis B vaccination (HepB) were followed up at 5 years after the primary immunization. A booster dose was given to those who had low hepatitis B surface antibody (anti-HBs) titers, defined as anti-HBs levels < 10 mIU/mL. Blood samples were collected at two weeks after the booster and anti-HBs levels were measured. We assumed those with ant-HBs levels > = 10 mIU/mL after the booster had anamnestic response. In total, 242 persons completed the booster and the anti-HBs test. The anamnestic response rate was 99.59% (241/242) and geometric mean concentration (GMC) of anti-HBs after the booster was 2989 mIU/mL (95% CI: 255, 35085). Anti-HBs titer after the booster dose had a positive correlation with anti-HBs titers measured right after the primary immunization as well as anti-HBs titers 5 years later just before the booster. After the booster, no significant difference was found in anti-HBs titers between participants who were immunized with the 10μg HepB vaccine and those with the 20μg vaccine. Multivariable analysis showed that 1) vaccine brand used for the primary vaccination, 2) anti-HBs titers after primary vaccination and 3) anti-HBs titers before the booster dose were independently associated with the anti-HBs titers after the booster 1) β = -0.21, 95% CI: -0.33, -0.09, P = 0.001; 2) β = 0.07, 95% CI: 0.05, 0.09, P < 0.001; 3) β = 0.04, 95% CI: 0.02, 0.07, P < 0.001). In summary, anamnestic response exists among almost all adults at five years after HepB primary immunization. Vaccine brand used for primary vaccination, initial anti-HBs titers after primary immunization and anti-HBs titers before the booster were the independent predictive factors of HepB anamnestic response titers.
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Affiliation(s)
- Wenlong Wu
- a School of Public Health, Shandong University , Jinan , China.,b Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention; Shandong Provincial Center for Disease Control and Prevention , Jinan , China
| | - Jingjing Lv
- a School of Public Health, Shandong University , Jinan , China.,b Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention; Shandong Provincial Center for Disease Control and Prevention , Jinan , China
| | - Jiaye Liu
- a School of Public Health, Shandong University , Jinan , China.,b Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention; Shandong Provincial Center for Disease Control and Prevention , Jinan , China
| | - Bingyu Yan
- a School of Public Health, Shandong University , Jinan , China.,b Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention; Shandong Provincial Center for Disease Control and Prevention , Jinan , China
| | - Yi Feng
- a School of Public Health, Shandong University , Jinan , China.,b Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention; Shandong Provincial Center for Disease Control and Prevention , Jinan , China
| | - Aiqiang Xu
- a School of Public Health, Shandong University , Jinan , China.,b Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention; Shandong Provincial Center for Disease Control and Prevention , Jinan , China
| | - Li Zhang
- a School of Public Health, Shandong University , Jinan , China.,b Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention; Shandong Provincial Center for Disease Control and Prevention , Jinan , China
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21
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Whitford K, Liu B, Micallef J, Yin JK, Macartney K, Van Damme P, Kaldor JM. Long-term impact of infant immunization on hepatitis B prevalence: a systematic review and meta-analysis. Bull World Health Organ 2018; 96:484-497. [PMID: 29962551 PMCID: PMC6022616 DOI: 10.2471/blt.17.205153] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 03/28/2018] [Accepted: 04/18/2018] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE To conduct a systematic review and meta-analysis of the long-term impact of infant vaccination on the prevalence of hepatitis B virus (HBV) infection at the population level. METHODS We searched online databases for articles reporting comparisons between population cohorts aged ≥ 15 years who were exposed or unexposed to infant HBV immunization programmes. We categorized programmes as universal or targeted to infants whose mothers were positive for hepatitis B surface antigen (HBsAg). We included studies reporting prevalence of hepatitis B core antibody (HBcAb), HBsAg, or both. We evaluated the quality of the study methods and estimated the relative reduction in the prevalence of infection. FINDINGS Of 26 studies that met the inclusion criteria, most were from China (20 studies). The prevalence of HBV infection in unvaccinated and universally vaccinated cohorts ranged from 0.6% (116 of 20 305 people) to 16.3% (60/367) and from 0.3% (1/300) to 8.5% (73/857), respectively. Comparing cohorts with universal vaccination to those without vaccination, relative prevalences were 0.24 (95% confidence interval, CI: 0.16-0.35) for HBsAg and 0.23 (95% CI: 0.17-0.32) for HBcAb. For populations with targeted vaccination, relative prevalences were 0.32 (95% CI: 0.24-0.43) and 0.33 (95% CI: 0.23-0.45), respectively. CONCLUSION The residual burden of infection in cohorts offered vaccination suggests that longer-term evaluations of vaccination coverage, timeliness and other aspects of programme quality are needed. As HBV-vaccinated infant cohorts reach adulthood, ongoing analysis of prevalence in adolescents and young adults will ensure that elimination efforts are on track.
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Affiliation(s)
- Kate Whitford
- Kirby Institute, Level 6, Wallace Wurth Building, UNSW Sydney, Kensington, Sydney, 2052 Australia
| | - Bette Liu
- School of Public Health and Community Medicine, UNSW Sydney, Sydney, Australia
| | - Joanne Micallef
- Kirby Institute, Level 6, Wallace Wurth Building, UNSW Sydney, Kensington, Sydney, 2052 Australia
| | - J Kevin Yin
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Kristine Macartney
- National Centre for Immunisation, Research and Surveillance, Sydney, Australia
| | - Pierre Van Damme
- Centre for the Evaluation of Vaccination, University of Antwerp, Antwerp, Belgium
| | - John M Kaldor
- Kirby Institute, Level 6, Wallace Wurth Building, UNSW Sydney, Kensington, Sydney, 2052 Australia
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22
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Özgüler M, Sayan M. Could resistant and escape variants of hepatitis B virus be a problem in the future? Future Virol 2018. [DOI: 10.2217/fvl-2017-0144] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Aim: Nucleos(t)ide analogs have a risk for the development of Polymerase gene mutations and they can cause compensatory mutations in the HBV surface gene. Alteration in the ‘a determinant’ of the s gene predispose for escape mutants. We aimed to evaluate primary, compensatory and escape mutations in chronic hepatitis B. Materials & methods: Two hundred nineteen specimens were obtained and HBV pol gene region was sequenced and amplified and HBV pol/s gene mutations were determined. Results: We detected primary mutation in 29.8% patients. Compensatory mutations were detected in 50.3%patients. Hepatitis B Immunoglobulin escape mutations, vaccine escape mutations, Hepatitis B diagnosis-escape and immunoselected amino acid substitutions were observed in 9.6%, 6.9%, 5.2% and 11.9% of patients, respectively. Antiviral drug-associated potential vaccine-escape mutants were detected in 17.9% patients. Conclusion: Therefore, epidemiological and demographical changes may be possible. Therefore, the typical HBsAg mutants and antiviral drug-associated potential vaccine-escape mutants should be monitored carefully.
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Affiliation(s)
- Müge Özgüler
- Department of Infectious Diseases & Clinical Microbiology, Elazığ Education & Research Hospital, Medical Sciences University, Elazığ, Turkey
| | - Murat Sayan
- PCR Unit, Faculty of Medicine, Clinical Laboratory, Kocaeli University, Kocaeli, Turkey
- Research Center of Experimental Health Sciences, Near East University, Nicosia, Northern Cyprus
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23
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Collier MG, Schillie S. Hepatitis B and Hepatitis D Viruses. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2018:1107-1114.e4. [DOI: 10.1016/b978-0-323-40181-4.00213-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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24
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25
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Anderson CL, Remschmidt C, Drobnitzky FP, Falkenhorst G, Zimmermann R, Wichmann O, Harder T. Hepatitis B immune status in adolescents vaccinated during infancy: A retrospective cohort study from a pediatric practice in Germany. Hum Vaccin Immunother 2017; 12:779-84. [PMID: 26633195 DOI: 10.1080/21645515.2015.1105414] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In Germany, vaccination of infants against hepatitis B is recommended since 1995. However, data on long-term immunity is sparse and the necessity of a booster dose remains uncertain. Aims of this study were to assess the long-term persistence of antibodies to the hepatitis B surface antigen (anti-HBs) after immunization during infancy and the effect of a subsequent hepatitis B booster vaccination during adolescence on anti-HBs levels. Patients from a private pediatric practice who had received a full vaccination course of hepatitis B as infants and who were quantitatively tested for anti-HBs during adolescence (pre-booster levels) were included. In those participants who received a hepatitis B booster, post-booster anti-HBs levels were measured. Univariate analyses were conducted to determine factors associated with pre- and post-booster anti-HBs levels, respectively. 106 participants (53% male) were included in the study. At an average of 13.7 y after primary vaccination, 14% of participants had an anti-HBs level of ≥100 IU/l, while 46% were at 10-99 IU/l and 40% had anti-HBs levels of <10 IU/l. In total, 34 received a booster vaccination. Of those, 97% (33/34) had post-booster anti-HBs levels ≥ 100 IU/l, which were independent from pre-booster levels. No other patient characteristics were associated with pre-booster or post-booster anti-HBs≥ 100 IU/l. Although almost half of study participants showed low anti-HBs levels at follow-up, robust responses to booster vaccination suggest that adolescents who received the full vaccination course during infancy are still protected against hepatitis B infection.
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Affiliation(s)
- Carrie L Anderson
- a Institute of Tropical Medicine and International Health, Charité-Universitätsmedizin Berlin , Berlin , Germany.,b Robert Koch Institute, Immunization Unit , Berlin , Germany
| | | | | | | | - Ruth Zimmermann
- d Robert Koch Institute, Unit for HIV/AIDS, STI and Blood-borne infections , Berlin , Germany
| | - Ole Wichmann
- b Robert Koch Institute, Immunization Unit , Berlin , Germany
| | - Thomas Harder
- b Robert Koch Institute, Immunization Unit , Berlin , Germany
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26
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Raymond SL, Rincon JC, Wynn JL, Moldawer LL, Larson SD. Impact of Early-Life Exposures to Infections, Antibiotics, and Vaccines on Perinatal and Long-term Health and Disease. Front Immunol 2017; 8:729. [PMID: 28690615 PMCID: PMC5481313 DOI: 10.3389/fimmu.2017.00729] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 06/08/2017] [Indexed: 12/21/2022] Open
Abstract
Essentially, all neonates are exposed to infections, antibiotics, or vaccines early in their lives. This is especially true for those neonates born underweight or premature. In contrast to septic adults and children who are at an increased risk for subsequent infections, exposure to infection during the neonatal period is not associated with an increased risk of subsequent infection and may be paradoxically associated with reductions in late-onset sepsis (LOS) in the most premature infants. Perinatal inflammation is also associated with a decreased incidence of asthma and atopy later in life. Conversely, septic neonates are at increased risk of impaired long-term neurodevelopment. While the positive effects of antibiotics in the setting of infection are irrefutable, prolonged administration of broad-spectrum, empiric antibiotics in neonates without documented infection is associated with increased risk of LOS, necrotizing enterocolitis, or death. Vaccines provide a unique opportunity to prevent infection-associated disease; unfortunately, vaccinations have been largely unsuccessful when administered in the first month of life with the exception of vaccines against hepatitis B and tuberculosis. Future vaccines will require the use of novel adjuvants to overcome this challenge. This review describes the influence of infections, antibiotics, and vaccines during the first days of life, as well as the influence on future health and disease. We will also discuss potential immunomodulating therapies, which may serve to train the preterm immune system and reduce subsequent infectious burden without subjecting neonates to the risks accompanied by virulent pathogens.
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Affiliation(s)
- Steven L Raymond
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Jaimar C Rincon
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - James L Wynn
- Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, United States
| | - Lyle L Moldawer
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Shawn D Larson
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
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Franzo G, Tucciarone CM, Cecchinato M, Drigo M. Porcine circovirus type 2 (PCV2) evolution before and after the vaccination introduction: A large scale epidemiological study. Sci Rep 2016; 6:39458. [PMID: 27991573 PMCID: PMC5171922 DOI: 10.1038/srep39458] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 11/21/2016] [Indexed: 01/02/2023] Open
Abstract
Since their commercialization, vaccines against Porcine circovirus type 2 (PCV2) have been the cornerstone control strategy. Nevertheless, the periodic emergence of new genotype waves and the recent reports of vaccine failure outbreaks have raised the question if widespread vaccination strategies could have driven viral evolution and affected different genotype fitness. To investigate this issue an in-deep analysis, based on a bioinformatics and biostatistics approach, has been implemented. ORF2 sequences from vaccinated and non-vaccinated populations (i.e. domestic pigs before and after vaccine introduction and wild boars) were considered. The action of selective forces on PCV2 strains has been analyzed and compared among groups. Remarkable differences were found in the selective forces acting on viral populations circulating in different “immune environments”. Particularly for PCV2a, a directional selection promoting a change in the viral capsid away from the vaccine specific antigenic determinants has been detected after vaccine introduction. Involved amino acids were previously reported to be part of viral epitopes whose variability is responsible of immune escape. Our findings support a change in PCV2 evolutionary pattern after widespread vaccination introduction and stress once more the compulsoriness of a continuous monitoring of PCV2 epidemiology to promptly act in response to the emergence of possible vaccine-escaping mutants.
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Wiedermann U, Garner-Spitzer E, Wagner A. Primary vaccine failure to routine vaccines: Why and what to do? Hum Vaccin Immunother 2016; 12:239-43. [PMID: 26836329 PMCID: PMC4962729 DOI: 10.1080/21645515.2015.1093263] [Citation(s) in RCA: 107] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
There are 2 major factors responsible for vaccine failures, the first is vaccine-related such as failures in vaccine attenuation, vaccination regimes or administration. The other is host-related, of which host genetics, immune status, age, health or nutritional status can be associated with primary or secondary vaccine failures. The first describes the inability to respond to primary vaccination, the latter is characterized by a loss of protection after initial effectiveness. Our studies concentrate on the evaluation of immunological characteristics responsible for primary vaccine failures in different (risk) populations for which the underlying mechanisms are currently unknown. Here we summarise current knowledge and findings from our studies. About 2–10% of healthy individuals fail to mount antibody levels to routine vaccines. Comparing the immune responses to different vaccines in non-responder and high-responder vaccinees revealed that hypo-responsiveness is antigen/vaccine-specific at the humoral but not at the cellular level. We found that T-regulatory as well as B-regulatory cells and the production of IL-10 are involved in non/hypo-responsiveness. Non-responsiveness increases with age and in particular vaccination to a novel vaccine in persons > 65 years is associated with a high low/non-responder rate, indicating that vaccine schedules and doses (at least for primary vaccination) should be adapted according to age. In light of the growing number of allergic but also obese people, our current studies concentrate on these risk groups to reveal whether different vaccination approaches are necessary for optimal protection compared to healthy individuals. These studies are in line with the significant paradigm shift taking place in many fields of medical research and care, and will extend the concept of personalised medicine into the field of vaccinology.
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Affiliation(s)
- Ursula Wiedermann
- a Institute of Specific Prophylaxis and Tropical Medicine; Medical University Vienna ; Vienna , Austria
| | - Erika Garner-Spitzer
- a Institute of Specific Prophylaxis and Tropical Medicine; Medical University Vienna ; Vienna , Austria
| | - Angelika Wagner
- a Institute of Specific Prophylaxis and Tropical Medicine; Medical University Vienna ; Vienna , Austria
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Schistosoma mansoni Infection Can Jeopardize the Duration of Protective Levels of Antibody Responses to Immunizations against Hepatitis B and Tetanus Toxoid. PLoS Negl Trop Dis 2016; 10:e0005180. [PMID: 27926921 PMCID: PMC5142771 DOI: 10.1371/journal.pntd.0005180] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 11/10/2016] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Schistosomiasis is a disease of major public health importance in sub-Saharan Africa. Immunoregulation begins early in schistosome infection and is characterized by hyporesponsiveness to parasite and bystander antigens, suggesting that a schistosome infection at the time of immunization could negatively impact the induction of protective vaccine responses. This study examined whether having a Schistosoma mansoni infection at the time of immunization with hepatitis B and tetanus toxoid (TT) vaccines impacts an individual's ability to achieve and maintain protective antibody levels against hepatitis B surface antigen or TT. METHODS Adults were recruited from Kisumu Polytechnic College in Western Kenya. At enrollment, participants were screened for schistosomiasis and soil transmitted helminths (STHs) and assigned to groups based on helminth status. The vaccines were then administered and helminth infections treated a week after the first hepatitis B boost. Over an 8 month period, 3 blood specimens were obtained for the evaluation of humoral and cytokine responses to the vaccine antigens and for immunophenotyping. RESULTS 146 individuals were available for final analysis and 26% were S. mansoni positive (Sm+). Schistosomiasis did not impede the generation of initial minimum protective antibody levels to either hepatitis B or TT vaccines. However, median hepatitis B surface antibody levels were significantly lower in the Sm+ group after the first boost and remained lower, but not significantly lower, following praziquantel (PZQ) treatment and final boost. In addition, 8 months following TT boost and 7 months following PZQ treatment, Sm+ individuals were more likely to have anti-TT antibody levels fall below levels considered optimal for long term protection. IL-5 levels in response to in vitro TT stimulation of whole blood were significantly higher in the Sm+ group at the 8 month time period as well. CONCLUSIONS Individuals with schistosomiasis at the start the immunizations were capable of responding appropriately to the vaccines as measured by antibody responses. However, they may be at risk of a more rapid decline in antibody levels over time, suggesting that treating schistosome infections with praziquantel before immunizations could be beneficial. The timing of the treatment as well as its full impact on the maintenance of antibodies against vaccine antigens remains to be elucidated.
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Cassaniti I, Calarota SA, Adzasehoun KMG, Chiesa A, Comolli G, Parea M, Baldanti F. Memory T cells specific for HBV enumerated by a peptide-based cultured enzyme-linked immunospot assay in healthy HBV-vaccinated subjects. Hum Vaccin Immunother 2016; 12:2927-2933. [PMID: 27392260 DOI: 10.1080/21645515.2016.1204500] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
Hepatitis B vaccine is the most effective strategy to control hepatitis B virus (HBV) infection and disease. It is considered that an anti-HBs (antibodies against HBV surface antigen) titer >10 mIU/ml, measured shortly after a complete vaccination schedule, provides protection against infection. Approximately 4-10% of healthy individuals fail to respond to 3-dose vaccination. Long-term HBV-specific memory T-cell response has not been fully investigated, mainly due to the lack of a suitable assay. We quantified HBV-specific expandable memory T cells by using a cultured IFN-γ enzyme-linked immunospot (ELISPOT) assay. Cultured ELISPOT response to an overlapping peptide pool representing the complete L (large) HBV envelope polypeptide was evaluated in 41 healthy subjects vaccinated 15-20 y earlier and 5 unvaccinated. Plasma samples were tested for anti-HBs. Vaccinated subjects had significantly higher HBV-specific T-cellular response than unvaccinated (p = 0.0002). HBV-specific T-cell response was mainly mediated by CD4+ T cells. No concordance was found between cultured ELISPOT and anti-HBs data in vaccinated subjects. Thirty-one (76%) vaccinated subjects were responders (anti-HBs >10 mIU/ml). Nineteen (46%) vaccinated subjects were considered to be responders in cultured ELISPOT. Twenty-two (54%) vaccinated subjects were considered non-responders in cultured ELISPOT; 5 of them (23%) were also humoral non-responders. About 12% of healthy HBV-vaccinated subjects are both humoral and cellular non-responders. Although the prognostic value of this assay has not been established in terms of predictability for susceptibility to de-novo HBV infection, ELISPOT data suggest that these subjects may be at risk for HBV infection and disease, especially health care workers.
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Affiliation(s)
- Irene Cassaniti
- a Department of Clinical, Surgical, Diagnostic and Pediatric Sciences , University of Pavia , Pavia , Italy
| | - Sandra A Calarota
- b Molecular Virology Unit, Microbiology and Virology Department , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
| | - Kodjo M G Adzasehoun
- b Molecular Virology Unit, Microbiology and Virology Department , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
| | - Antonella Chiesa
- b Molecular Virology Unit, Microbiology and Virology Department , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
| | - Giuditta Comolli
- b Molecular Virology Unit, Microbiology and Virology Department , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.,c Experimental Research Laboratories , Biotechnology Area, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
| | - Maurizio Parea
- b Molecular Virology Unit, Microbiology and Virology Department , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
| | - Fausto Baldanti
- a Department of Clinical, Surgical, Diagnostic and Pediatric Sciences , University of Pavia , Pavia , Italy.,b Molecular Virology Unit, Microbiology and Virology Department , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
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Poorolajal J, Hooshmand E, Cochrane Hepato‐Biliary Group. Booster dose vaccination for preventing hepatitis B. Cochrane Database Syst Rev 2016; 2016:CD008256. [PMID: 27271960 PMCID: PMC7154826 DOI: 10.1002/14651858.cd008256.pub3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Antibodies against hepatitis B surface antigen (HBsAg) wane over time following hepatitis B immunisation; hence, it is unclear whether people vaccinated in three-dose or four-dose schedules of the hepatitis B vaccine are still immune when the hepatitis B surface antibody (anti-HBs) level in their body is undetectable, or lower than the level usually considered protective. This question may potentially be answered indirectly by measuring the anamnestic immune response to a booster dose of vaccine. The term 'booster' (or revaccination) refers to an additional dose of hepatitis B vaccine (HBV) given some time post-primary vaccination to induce immune memory and improve protection against hepatitis B virus (HBV) infection. OBJECTIVES To assess the benefits and harms of booster dose hepatitis B vaccination, more than five years after the primary vaccination, for preventing HBV infection in healthy individuals previously vaccinated with the hepatitis B vaccine, and with hepatitis B surface antibody (anti-HBs) levels below 10 mIU/mL. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, conference databases, and reference lists of articles to January 2016. We also contacted authors of articles. In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (May 2016). SELECTION CRITERIA Randomised clinical trials addressing anamnestic immune response to a booster dose of hepatitis B vaccine, more than five years after the primary vaccination, in apparently healthy participants, vaccinated in a three-dose or four-dose schedule of the hepatitis B vaccine during the primary vaccination, without receiving an additional dose or immunoglobulin. DATA COLLECTION AND ANALYSIS Both review authors decided if the identified studies met the inclusion criteria or not. Primary outcomes included the proportion of participants with anamnestic immune response in non-protected participants and signs of HBV infection. Secondary outcomes were the proportion of participants that developed local and systemic adverse events following a booster dose injection. We planned to report the weighted proportion with 95% confidence intervals (CIs). MAIN RESULTS There were no eligible randomised clinical trials fulfilling the inclusion criteria of this review. AUTHORS' CONCLUSIONS We were unable to include any randomised clinical trials on the topic; only randomised clinical trials will be able to provide an answer as to whether a booster dose vaccination is able to protect against hepatitis B infection.
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Affiliation(s)
- Jalal Poorolajal
- School of Public Health, Hamadan University of Medical SciencesModeling of Noncommunicable Diseases Research Center, Department of EpidemiologyShahid Fahmideh AveHamadanHamadanIran6517838695
| | - Elham Hooshmand
- School of Public Health, Hamadan University of Medical SciencesDepartment of EpidemiologyHamadanIran
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Liu J, Feng Y, Wang J, Li X, Lei C, Jin D, Feng W, Yang Y, He Y, Li Y, Du D, Zhang X, Jin L, Yan T, Chen T, Zhao Y. An "immune barrier" is formed in the placenta by hepatitis B immunoglobulin to protect the fetus from hepatitis B virus infection from the mother. Hum Vaccin Immunother 2016; 11:2068-76. [PMID: 26126021 PMCID: PMC4635728 DOI: 10.1080/21645515.2015.1010890] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The effect of hepatitis B immunoglobulin (HBIG) on hepatitis B virus (HBV) DNA load and its protective mechanism are not well understood. Twenty-eight hepatitis B surface antigen (HBsAg)–positive pregnant women and their newborns were assigned to an experimental (n = 12) or control group (n = 16) according to whether they received HBIG during pregnancy. HBV DNA load and markers titer of the mothers and newborns were tested. These markers and HBV DNA load in mothers of the experimental group did not fluctuate significantly and were comparable to the control. In the experimental group, there was a positive correlation between mothers and their newborns with regard to hepatitis B surface antibody titer. Immunohistochemical staining of placenta sections showed that HBsAg-positive areas mainly included trophoblastic cells and villous mesenchymal cells without HBIG colocalization, whereas HBIG-positive areas principally included villous capillary endothelial cells and villous mesenchymal cells. Additionally, compared with the control group, the positive rate and mean density of HBIG in the experimental group were remarkably higher. HBIG deposition was seen in Hofbauer cells. Thus, rather than influencing virus replication, HBIG forms an immune barrier between the mother and fetus to prevent HBV transmission.
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Affiliation(s)
- Jinfeng Liu
- a Department of Infectious Diseases ; the First Affiliated Hospital of Medical College; Xi'an Jiaotong University ; Xi'an , Shaanxi Province , China
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Qawasmi M, Samuh M, Glebe D, Gerlich WH, Azzeh M. Age-dependent decrease of anti-HBs titers and effect of booster doses using 2 different vaccines in Palestinian children vaccinated in early childhood. Hum Vaccin Immunother 2016; 11:1717-24. [PMID: 25996579 DOI: 10.1080/21645515.2015.1041687] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Immunization against hepatitis B virus (HBV) has proven to be highly effective and led to significant reduction of new infections worldwide. However, protective immunity measured by anti-HBs titers may decrease to critical levels in the years after basal immunization, particularly in case of exposure to HBV variants different from the vaccine strain. We tested 400 Palestinian children between one and 19 years of age for their anti-HBs titer, challenged the immune memory of those with low or absent anti-HBs with 2 types of hepatitis B vaccines and determined thereafter the anti-HBs titer. At the age of one, 92.2% of the children presented with protective anti-HBs titers (≥ 10 mIU/ml) with the majority having ≥ 100 mIU/ml. Protective immunity was still high at ages 2 (87.5%) and 4 (95%), declining by age 5 and 6 (from 69.2% to 66.7%) and down to an average of 39.8% between the ages of 7 and 19. 160 children with a nonprotective or low immune response challenged with either the yeast-derived Engerix-B or the mammalian cell-derived preS1-containing Sci-B-Vac vaccine showed an anamnestic immune response. 92.4% and 85.9% of the children challenged with one dose Sci-B-Vac and Engerix-B presented with anti-HBs titers >100 mIU/ml respectively. Our results reveal that vaccine-induced protective anti-HBs titers against HBV decrease rapidly beyond the age of 6 in Palestinian children, but can be strongly enhanced with a single booster vaccine dose, independent of brand and antigen composition. Our data suggest that a booster vaccine dose against HBV during school years may be useful.
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Affiliation(s)
- Mohammad Qawasmi
- a Virology Research Laboratory; Medical Research Center; Al-Quds University ; Abu Dies-East Jerusalem, Palestine
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Yin Y, Zhang P, Tan Z, Zhou J, Wu L, Hou H. The Association of Pre-S/S Gene Mutations and Hepatitis B Virus Vertical Transmission. HEPATITIS MONTHLY 2016; 16:e32160. [PMID: 27226799 PMCID: PMC4876664 DOI: 10.5812/hepatmon.32160] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Revised: 12/01/2015] [Accepted: 01/24/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND HBV Pre-S/S gene mutations can occur before or after implementation of combined vaccination program. HBV Prs-S/S gene mutation is a risk factor of vaccination failure and frequently causes HBV vertical transfection. OBJECTIVES To assess the association of hepatitis B virus (HBV) S gene mutations with vertical transmission. PATIENTS AND METHODS In this prospective nested case-control study, a total of 60 pregnant women with positive serum HBsAg and HBV DNA ≥ 10(7) IU/mL were divided into a case group (15 cases with vaccination failure) and a control group (45 cases with vaccination success) according to whether their infants tested positive for HBV infection. Mothers and their children in the case group were further sub-divided into groups including mothers, newborns and infant (the same newborns at age of seven months). The pre-S/S gene mutations were detected by PCR and sequenced and its association with vertical transmission of HBV was analyzed. RESULTS HBV genotype B was the dominant genotype in the both groups' mothers. Each mother-child pair in case group had the same HBV genotype. There were no significant differences in mutation frequencies of HBV Pre-S/S gene between case and control groups' mothers (Fragment 1 (M): 2 vs. 4, P > 0.05; Fragment 2 (M): 10 vs. 10, P > 0.05), or among the mothers, newborns and infants in the case group (Fragment 1 (M): 2, 2, and 3, respectively, P > 0.05; Fragment 2 (M): 10, 10 and 10 respectively, P > 0.05). Mutation site analysis of the both groups' mothers demonstrated 108 different mutation sites in the HBV pre-S/S gene, with 105 silent mutations and 5 missense mutations including ntA826G, ntC531T, ntT667C, ntC512T and ntC546A. Among 15 mother-newborn-infant pairs with successful PCR and sequence in case group, 7 (41.17%) mother-newborn pairs, 9 (60.00%) mother-infant pairs and 3 (20.00%) infant-newborn pairs had different mutation sites. CONCLUSIONS HBV in children due to vaccination failure was resulted from vertical transmission. HBV Pre-S/S gene mutations were prevalent and could occur before or after vaccination. Therefore, simply analyzing mutation frequency of HBV gene was not of value. To advance blocking HBV vertical transmission, future studies should focus on specific mutation sites, potentially associated with vaccination failure.
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Affiliation(s)
- Yuzhu Yin
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
- Corresponding Author: Yuzhu Yin, Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, P. O. Box: 510630, Guangzhou, China. Tel: +86-18620174975, Fax: +86-2085253040, E-mail:
| | - Peizhen Zhang
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zhangmin Tan
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jin Zhou
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Lingling Wu
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Hongying Hou
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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Arias-Moliz MT, Rojas L, Liébana-Cabanillas F, Bernal C, Castillo F, Rodríguez-Archilla A, Castillo A, Liébana J. Serologic control against hepatitis B virus among dental students of the University of Granada, Spain. Med Oral Patol Oral Cir Bucal 2015; 20:e566-71. [PMID: 26241457 PMCID: PMC4598925 DOI: 10.4317/medoral.20579] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2015] [Accepted: 04/04/2015] [Indexed: 12/12/2022] Open
Abstract
Background To evaluate the immunological situation against hepatitis B virus (HBV) of a cohort of dentistry students, to analyze the behavior of the levels of hepatitis B surface antigen (anti-HBs) after the administration of one or three vaccine doses, and to determine the influence of age and sex on the immune response. Material and Methods This retrospective cohort study included students attending the School of Dentistry of the institution where the study was performed from 2005 to 2012 who had completed the public health vaccination calendar for HBV at the age of 12-13. Data on age, sex, basal anti-HBs levels, post-vaccination anti-HBs results and final anti-HBs levels were collected. Comparisons of the basal and final levels, as well as associations regarding age and sex, were performed by means of the Student t and Chi-square tests. Results Of the 359 students, 97 (27.02%) had basal antibody concentrations <10 mIU/ml, whereas in 262 the levels of anti-HBs were ≥10 mIU/ml (72.98%). Of the 288 participating students who completed the School´s protocol for immunization, 287 (99.65%) attained a level of protection ≥10 mIU/ml. Globally, there were statistically significant differences between the basal antibody levels and those achieved after administration of the vaccine and booster, but no association with age or sex was observed. Conclusions About 70% of dental students vaccinated as preadolescents had serologic evidence of protection against HBV. Administering a booster is associated with the presence of an excellent immune memory. There is clearly a need to reinforce control of the antibody levels in groups at risk, such as Dentistry students. Key words:Dental students, hepatitis B virus, serologic control.
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Affiliation(s)
- M-T Arias-Moliz
- Department of Microbiology, School of Dentistry, Campus de Cartuja, Colegio Máximo s/n, E-18071 Granada, Spain,
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Kang G, Ma F, Chen H, Yang Y, Guo S, Wang Z, Liang X, Li L, Cui F, Zhang L. Efficacy of antigen dosage on the hepatitis B vaccine response in infants born to hepatitis B-uninfected and hepatitis B-infected mothers. Vaccine 2015; 33:4093-9. [DOI: 10.1016/j.vaccine.2015.06.081] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Revised: 05/19/2015] [Accepted: 06/22/2015] [Indexed: 01/27/2023]
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Li X, Wiesen E, Diorditsa S, Toda K, Duong TH, Nguyen LH, Nguyen VC, Nguyen TH. Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection. Vaccine 2015; 34:869-73. [PMID: 26055296 PMCID: PMC5357724 DOI: 10.1016/j.vaccine.2015.05.067] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Revised: 05/13/2015] [Accepted: 05/26/2015] [Indexed: 12/17/2022]
Abstract
Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine.
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Affiliation(s)
- Xi Li
- Johns Hopkins University, Candidate for Master of Science in Public Health, 615 N. Wolfe St., Baltimore, MD 21205, United States
| | - Eric Wiesen
- Expanded Programme on Immunization Unit, World Health Organization, Western Pacific Regional Office, PO Box 2932, Manila, Philippines.
| | - Sergey Diorditsa
- Expanded Programme on Immunization Unit, World Health Organization, Western Pacific Regional Office, PO Box 2932, Manila, Philippines
| | - Kohei Toda
- Expanded Programme on Immunization Unit, World Health Organization Country Office, 63 Tran Hung Dao Street, Hoan Kiem District, Ha Noi, Viet Nam
| | - Thi Hong Duong
- National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hai Ba Trung, Ha Noi 10000, Viet Nam
| | - Lien Huong Nguyen
- National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hai Ba Trung, Ha Noi 10000, Viet Nam
| | - Van Cuong Nguyen
- National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hai Ba Trung, Ha Noi 10000, Viet Nam
| | - Tran Hien Nguyen
- National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hai Ba Trung, Ha Noi 10000, Viet Nam
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Trevisan A, Nicolli A, Chiara F. Hepatitis B: prevention, protection and occupational risk. Future Virol 2015. [DOI: 10.2217/fvl.14.90] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
ABSTRACT Since 1992, the inclusion of HBV vaccination has been recommended by the WHO for all immunization programs implemented by nations. In Europe, the introduction of HBV vaccination has markedly reduced the incidence of acute HBV, and before the introduction of HBV vaccine, healthcare workers (HCW) were at considerable risk of infection. The present review discusses the main problems regarding three fundamental issues in hospital settings: prevention of HBV in HCW, protection induced by vaccination (problems regarding nonresponders) and risk for HCW exposed to blood-borne pathogens (occupational risk). The screening of HBV markers plays a decisive role in evaluating the degree of immune coverage in subjects exposed to biological risk and permits an increase in immune coverage through vaccine implementation.
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Affiliation(s)
- Andrea Trevisan
- Department of Cardiologic, Thoracic & Vascular Sciences, University of Padova, Via Giustiniani 2, I-35128 Padova, Italy
| | - Annamaria Nicolli
- Department of Cardiologic, Thoracic & Vascular Sciences, University of Padova, Via Giustiniani 2, I-35128 Padova, Italy
| | - Federica Chiara
- Department of Cardiologic, Thoracic & Vascular Sciences, University of Padova, Via Giustiniani 2, I-35128 Padova, Italy
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Goyal A, Murray JM. The impact of vaccination and antiviral therapy on hepatitis B and hepatitis D epidemiology. PLoS One 2014; 9:e110143. [PMID: 25313681 PMCID: PMC4196970 DOI: 10.1371/journal.pone.0110143] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 09/17/2014] [Indexed: 12/18/2022] Open
Abstract
The major cause of liver cancer around the globe is hepatitis B virus (HBV), which also contributes to a large number of deaths due to liver failure alone. Hepatitis delta virus (HDV) is as potentially alarming as HBV since life threatening cases are 10 times more likely with HBV-HDV dual infection compared to HBV monoinfection. So far, there is no established effective treatment against HDV and the only preventive action suggested by the World Health Organization is to introduce HBV vaccination for children immediately after birth (newborns) and thus reduce the available pool for HDV infection. Here the main objective is to understand the complex dynamics of HBV-HDV infection in a human population that can inform public health policy makers on the level of different preventive measures required to eliminate HBV and HDV infections. Model simulations suggest that HBV vertical transmission and HBV vaccination rates for newborns are instrumental in determining HBV and HDV prevalence. A decrease in HBV prevalence is observed as vaccination coverage increases and it is possible to eradicate both HBV and HDV using high vaccination coverage of ≥80% in the long term. We further found that HDV presence results in lower HBV prevalence. An application of our model to China revealed that vaccinating every newborn in China will further prevent 1.69 million new infections by 2028 as compared to the current 90% vaccination coverage. Although, higher vaccination coverage of newborns should eliminate both HBV and HDV over a long time period, any short term strategy to eradicate HDV must include additional preventive measures such as HBV adult vaccination. Implementation of HBV adult vaccination programs at a rate of 10% per year over 15 years will further prevent 39 thousand new HDV infections in China by 2028 as compared to HBV vaccination programs solely for newborns.
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Affiliation(s)
- Ashish Goyal
- School of Mathematics and Statistics, University of New South Wales, Sydney, Australia
- * E-mail:
| | - John M. Murray
- School of Mathematics and Statistics, University of New South Wales, Sydney, Australia
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Saffar H, Saffar MJ, Ajami A, Khalilian AR, Shams-Esfandabad K, Mirabi AM. Long-term T-cell-mediated immunologic memory to hepatitis B vaccine in young adults following neonatal vaccination. HEPATITIS MONTHLY 2014; 14:e22223. [PMID: 25368659 PMCID: PMC4214124 DOI: 10.5812/hepatmon.22223] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Revised: 08/20/2014] [Accepted: 08/29/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND The long-term duration of cell-mediated immunity induced by neonatal hepatitis B virus (HBV) vaccination is unknown. OBJECTIVES Study was designed to determine the cellular immunity memory status among young adults twenty years after infantile HB immunization. PATIENTS AND METHODS Study subjects were party selected from a recent seroepidemiologic study in young adults, who had been vaccinated against HBV twenty years earlier. Just before and ten to 14 days after one dose of HBV vaccine booster injection, blood samples were obtained and sera concentration of cytokines (interleukin 2 and interferon) was measured. More than twofold increase after boosting was considered positive immune response. With regard to the serum level of antibody against HBV surface antigen (HBsAb) before boosting, the subjects were divided into four groups as follow: GI, HBsAb titer < 2; GII, titer 2 to 9.9; GIII, titer 10 to 99; and GIV, titers ≥ 100 IU/L. Mean concentration level (MCL) of each cytokines for each group at preboosting and postboosting and the proportion of responders in each groups were determined. Paired descriptive statistical analysis method (t test) was used to compare the MCL of each cytokines in each and between groups and the frequency of responders in each group. RESULTS Before boosting, among 176 boosted individuals, 75 (42.6%) had HBsAb 10 IU/L and were considered seroprotected. Among 101 serosusceptible persons, more than 80% of boosted individuals showed more than twofold increase in cytokines concentration, which meant positive HBsAg-specific cell-mediated immunity. MCL of both cytokines after boosting in GIV were decreased more than twofold, possibly because of recent natural boosting. CONCLUSIONS Findings showed that neonatal HBV immunization was efficacious in inducing long-term immunity and cell-mediated immune memory for up to two decades, and booster vaccination are not required. Further monitoring of vaccinated subjects for HBV infections are recommended.
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Affiliation(s)
- Hiva Saffar
- Department of Pathology, Shariaty Hospital, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Mohammed Jafar Saffar
- Department of Pediatric Infectious Diseases Ward, Boali-Sina Hospital and Antimicrobial Resistant Nosocomial Infection Research Center, Mazandaran University of Medical Sciences, Sari, IR Iran
| | - Abolghasem Ajami
- Molecular and Cell-Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, IR Iran
| | - Ali Reza Khalilian
- Department of Biostatistics, Mazandaran University of Medical Sciences, Sari, IR Iran
| | - Kian Shams-Esfandabad
- Department of Pathology, Shariaty Hospital, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Araz Mohammad Mirabi
- Molecular and Cell-Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, IR Iran
- Corresponding Author: Araz Mohammad Mirabi, Department of Immunology, Mazandaran University of Medical Sciences, Sari, IR Iran. Tel: +98-1133344506, Fax: +98-1133344506, E-mail:
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Keck JW, Bulkow LR, Raczniak GA, Negus SE, Zanis CL, Bruce MG, Spradling PR, Teshale EH, McMahon BJ. Hepatitis B virus antibody levels 7 to 9 years after booster vaccination in Alaska native persons. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2014; 21:1339-42. [PMID: 25056363 PMCID: PMC4178570 DOI: 10.1128/cvi.00263-14] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 07/17/2014] [Indexed: 01/05/2023]
Abstract
Hepatitis B antibody persistence was assessed in individuals who had previously received a vaccine booster. We measured hepatitis B surface antigen antibody (anti-HBs) levels 7 to 9 years post-hepatitis B booster in individuals with primary vaccination at birth. While 95 (91.3%) of 104 participants had detectable anti-HBs (minimum, 0.1 mIU/ml; maximum, 1,029 mIU/ml), only 43 (41%) had protective levels of ≥10 mIU/ml. Pre- and week 4 postbooster anti-HBs levels were significant predictors of hepatitis B immunity at follow-up (P < 0.001). Almost all participants had detectable anti-HBs 7 to 9 years after the hepatitis B vaccine booster, but less than half had levels ≥10 mIU/ml.
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Affiliation(s)
- James W Keck
- Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Arctic Investigations Program, Centers for Disease Control and Prevention, Anchorage, Alaska, USA
| | - Lisa R Bulkow
- Arctic Investigations Program, Centers for Disease Control and Prevention, Anchorage, Alaska, USA
| | - Gregory A Raczniak
- Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Arctic Investigations Program, Centers for Disease Control and Prevention, Anchorage, Alaska, USA
| | - Susan E Negus
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA
| | - Carolyn L Zanis
- Arctic Investigations Program, Centers for Disease Control and Prevention, Anchorage, Alaska, USA
| | - Michael G Bruce
- Arctic Investigations Program, Centers for Disease Control and Prevention, Anchorage, Alaska, USA
| | - Philip R Spradling
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Eyasu H Teshale
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Brian J McMahon
- Arctic Investigations Program, Centers for Disease Control and Prevention, Anchorage, Alaska, USA Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA
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Avdicova M, Crasta PD, Hardt K, Kovac M. Lasting immune memory against hepatitis B following challenge 10-11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11-12 months of age. Vaccine 2014; 33:2727-33. [PMID: 24962750 DOI: 10.1016/j.vaccine.2014.06.070] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2012] [Revised: 05/21/2014] [Accepted: 06/13/2014] [Indexed: 01/05/2023]
Abstract
BACKGROUND The combined hexavalent diphtheria-tetanus-pertussis-hepatitis B-inactivated poliomyelitis - Haemophilus influenzae type b conjugate vaccine (Infanrix hexa™; DTPa-HBV-IPV/Hib: GlaxoSmithKline Vaccines) induces robust responses to the HBV component when administered at 3, 5 and 11-12 months of age. We assessed long term HBV antibody persistence 10-11 years after primary vaccination in infancy. METHODS Antibody persistence and immune memory were assessed post-primary vaccination at 3, 5, 11-12 months with DTPa-HBV-IPV/Hib, or monovalent HBV vaccine (Engerix™ B, GlaxoSmithKline Vaccines) co-administered with DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in 185 children aged 11-12 years. Blood samples were collected before and 1 month after a challenge dose of Engerix™ B (10μg dose). RESULTS 10-11 years after primary vaccination the percentage of subjects with persisting anti-HBs antibody concentrations ≥10mIU/ml was 48.4% in the DTPa-HBV-IPV/Hib group and 58.4% in the DTPa-IPV/Hib+HBV group. After the HBV challenge dose, the percentage with anti-HBs ≥100mIU/ml increased from 14.7% to 93.6% in the DTPa-HBV-IPV/Hib group and 19.1% to 94.4% in the DTPa-IPV/Hib+HBV group. Anti-HBs GMCs increased by at least 187-fold in each group. An anamnestic response (≥4-fold increase in initially seropositive or anti-HBs concentration ≥10mIU/ml in initially seronegative subjects) was observed in 96.8% and 96.6% of subjects in the DTPa-HBV-IPV/Hib and DTPa-IPV/Hib+HBV groups, respectively. No serious adverse events occurred that were considered related to challenge vaccination. CONCLUSION Administration of HBV as part of a combination vaccine or as a monovalent vaccine induced long lasting immune memory against HBV in children primed at 3, 5 and 11 months of age. Antibody persistence and immune memory were similar, suggesting that protection afforded by DTPa-HBV-IPV/Hib and monovalent HBV vaccines, is likely to be of similar duration. The administration of HBV challenge dose 10-11 years after the 3, 5, 11-12 months primary schedule induced strong anamnestic responses and was well tolerated. This study is registered at www.clinicaltrials.govNCT01138098.
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Affiliation(s)
- Mária Avdicova
- Cesta Knemocnici 1, RÚVZ Banská Bystrica (úvz), Slovakia.
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Spada E, Romanò L, Tosti ME, Zuccaro O, Paladini S, Chironna M, Coppola RC, Cuccia M, Mangione R, Marrone F, Negrone FS, Parlato A, Zamparo E, Zotti CM, Mele A, Zanetti AR. Hepatitis B immunity in teenagers vaccinated as infants: an Italian 17-year follow-up study. Clin Microbiol Infect 2014; 20:O680-6. [PMID: 24528380 DOI: 10.1111/1469-0691.12591] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2013] [Revised: 01/30/2014] [Accepted: 02/09/2014] [Indexed: 01/05/2023]
Abstract
We assessed the persistence of hepatitis B surface antigen antibody (anti-HBs) and immune memory in a cohort of 571 teenagers vaccinated against hepatitis B as infants, 17 years earlier. Vaccinees were followed-up in 2003 and in 2010 (i.e. 10 years and 17 years after primary vaccination, respectively). When tested in 2003, 199 vaccinees (group A) had anti-HBs <10 mIU/mL and were boosted, 372 (group B) were not boosted because they had anti-HBs ≥10 mIU/mL (n = 344) or refused booster (n = 28) despite anti-HBs <10 mIU/mL. In 2010, 72.9% (416/571) of participants had anti-HBs ≥10 mIU/mL (67.3% in group A vs. 75.8% in group B; p 0.03). The geometric mean concentrations (GMCs) were similar in both groups. Between 2003 and 2010, anti-HBs concentrations in previously boosted individuals markedly declined with GMC dropping from 486 to 27.7 mIU/mL (p <0.001). Fifteen vaccinees showed a marked increase of antibody, possibly due to natural booster. In 2010, 96 individuals (37 of group A and 59 of group B) with anti-HBs <10 mIU/mL were boosted; all vaccinees of the former group and all but two of the latter had an anamnestic response. Post-booster GMC was higher in group B (895.6 vs. 492.2 mIU/mL; p 0.039). This finding shows that the immune memory for HBsAg persists beyond the time at which anti-HBs disappears, conferring long-term protection.
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Affiliation(s)
- E Spada
- Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto Superiore di Sanitá, Rome; Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Rome
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De Schryver A, Claesen B, Meheus A, Hambach R, van Sprundel M, François G. Hepatitis B vaccination policies for student healthcare workers in Europe. J Hosp Infect 2014; 86:147-50. [DOI: 10.1016/j.jhin.2013.11.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Accepted: 11/15/2013] [Indexed: 10/25/2022]
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Abstract
A new hepatitis B vaccine (FENDrix, GlaxoSmithKline Biologicals) containing as active substance 20 microg of recombinant hepatitis B virus surface antigen produced in Saccharomyces cerevisiae has recently been licensed in Europe. It is prepared with a novel adjuvant system: aluminum phosphate and 3-O-desacyl-4 -monophosphoryl lipid A. It is intended for use in adults from the age of 15 years onwards for active immunization against hepatitis B virus infection for patients with renal insufficiency (including prehemodialysis and hemodialysis patients). It is applied in a four-dose scheme: day 0, month 1, 2 and 6 after day 0. Due to the improved adjuvant system it induces higher antibody concentrations that reach protective levels in a faster fashion. Furthermore, due to higher titers reached after the primary immunization course, protective levels are retained for a longer period of time. Vaccination with FENDrix induces more transient local symptoms, with pain at the injection site being the most frequently reported solicited local symptom. Other symptoms such as fatigue, gastrointestinal disorders and headaches were also frequently observed but resolved without sequelae. The higher risk of hepatitis B transmission in patients with end-stage renal disease and the often immunocompromised status of these patients afford a tailored vaccination strategy that, up to now, has consisted of injecting double doses of ordinary hepatitis B vaccines. With the introduction of FENDrix there now exists an efficient alternative with superior immunogenicity that is, despite comparatively higher reactogenicity, well tolerated.
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Affiliation(s)
- Michael Kundi
- Center for Public Health, Medical University of Vienna, Vienna, Austria.
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48
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Bagheri-Jamebozorgi M, Keshavarz J, Nemati M, Mohammadi-Hossainabad S, Rezayati MT, Nejad-Ghaderi M, Jamalizadeh A, Shokri F, Jafarzadeh A. The persistence of anti-HBs antibody and anamnestic response 20 years after primary vaccination with recombinant hepatitis B vaccine at infancy. Hum Vaccin Immunother 2014; 10:3731-6. [PMID: 25483689 PMCID: PMC4514033 DOI: 10.4161/hv.34393] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Revised: 07/25/2014] [Accepted: 08/08/2014] [Indexed: 01/16/2023] Open
Abstract
Hepatitis B (HB) vaccine induces protective levels of antibody response (anti-HBs≥10 mIU/mL) in 90-99% of vaccinees. The levels of anti-HBs antibody decline after vaccination. The aim of this study was to evaluate the persistence of anti-HBs antibodies and immunologic memory in healthy adults at 20 years after primary vaccination with recombinant HB vaccine. Blood samples were collected from 300 adults at 20 years after primary HB vaccination and their sera were tested for anti-HBs antibody by ELISA technique. A single booster dose of HB vaccine was administered to a total of 138 subjects, whose anti-HBs antibody titer was <10 mIU/mL. The sera of subjects were re-tested for the anti-HBs antibody levels at 4 weeks after booster vaccination. At 20 years after primary vaccination 37.0% of participants had protective levels of antibody with geometric mean titer (GMT) of 55.44±77.01 mIU/mL. After booster vaccination, 97.1% of vaccinees developed protective levels of antibody and the GMT rose from 2.35±6.49 mIU/mL to 176.28±161.78 mIU/mL. 125/138 (90.6%) of re-vaccinated subjects also showed an anamnestic response to booster vaccination. At 20 years after primary vaccination with HB vaccine, low proportion of the subjects had protective levels of antibody. However, the majority of the re-vaccinated subjects developed protective levels of anti-HBs and showed an anamnestic response after booster vaccination. Additional follow-up studies are necessary to determine the duration of immunological memory.
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Key Words
- Anti-HBc antibody, antibody to HBcAg
- Anti-HBs antibody, antibody to HBsAg
- ELISA, Enzyme-linked immunosorbent assay
- EPI, Expanded Program on Immunization
- GMT, Geometric mean titer
- HB, Hepatitis B
- HBV, Hepatitis B virus
- HBcAg, Hepatitis B core antigen
- HBsAg, Hepatitis B surface antigen
- WHO, World Health Organization
- anamnestic response
- anti-HBs antibody
- hepatitis B vaccine
- mIU/mL, milli-international units per milliliter
- persistence
- protection
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Affiliation(s)
- Masoomeh Bagheri-Jamebozorgi
- Molecular Medicine Research Center; Rafsanjan University of Medical Sciences; Rafsanjan, Iran
- Department of Immunology; School of Medicine; Rafsanjan University of Medical Sciences; Rafsanjan, Iran
| | - Jila Keshavarz
- Molecular Medicine Research Center; Rafsanjan University of Medical Sciences; Rafsanjan, Iran
- Department of Immunology; School of Medicine; Rafsanjan University of Medical Sciences; Rafsanjan, Iran
| | - Maryam Nemati
- Department of Immunology; School of Medicine; Kerman University of Medical Sciences; Kerman, Iran
| | | | - Mohammad-Taghi Rezayati
- Department of Immunology; School of Medicine; Rafsanjan University of Medical Sciences; Rafsanjan, Iran
| | - Mohsen Nejad-Ghaderi
- Health Vice-Chancellor; Rafsanjan University of Medical Sciences; Rafsanjan, Iran
| | - Ahmad Jamalizadeh
- Health Vice-Chancellor; Rafsanjan University of Medical Sciences; Rafsanjan, Iran
| | - Fazel Shokri
- Department of Immunology; School of Public Health; Tehran University of Medical Sciences; Tehran, Iran
| | - Abdollah Jafarzadeh
- Molecular Medicine Research Center; Rafsanjan University of Medical Sciences; Rafsanjan, Iran
- Department of Immunology; School of Medicine; Rafsanjan University of Medical Sciences; Rafsanjan, Iran
- Department of Immunology; School of Medicine; Kerman University of Medical Sciences; Kerman, Iran
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Ang LW, Cutter J, James L, Goh KT. Seroepidemiology of hepatitis B virus infection among adults in Singapore: a 12-year review. Vaccine 2013; 32:103-10. [PMID: 24200974 DOI: 10.1016/j.vaccine.2013.10.057] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 10/08/2013] [Accepted: 10/16/2013] [Indexed: 02/06/2023]
Abstract
We undertook a national hepatitis B seroprevalence study to assess the seroprevalence of hepatitis B virus (HBV) markers in the adult population in Singapore in 2010 and make comparisons with the seroprevalence in 1998 and 2004. The study involved residual sera from national health surveys conducted every six years since 1998. The tests for HBV markers were carried out using commercial chemiluminescent microparticle immunoassay. In 2010, the prevalence of hepatitis B surface antigen (HBsAg) among 3293 Singapore residents aged 18-79 years was 3.6% (95% confidence interval [CI] 2.9-4.2%). Hepatitis B e antigen (HBeAg) was detected in 4.2% of those who were HBsAg positive. About 22.5% (95% CI 21.1-23.9%) were positive for antibody to hepatitis B core antigen (anti-HBc). The overall population immunity to HBV, as determined by antibody to hepatitis B surface antigen (anti-HBs)≥ 10 mIU/mL, was 43.9% (95% CI 42.2-45.6%). Among young adults below 30 years of age, HBsAg prevalence (1.1%) was half that in 1998 and 2004, and in those positive for HBsAg, none was positive for HBeAg in 2010, compared to 20.8% in 1998 and 15.8% in 2004. In this age group, anti-HBc prevalence also decreased significantly from 22.1% in 2004 to 4.4% in 2010, while anti-HBs (≥ 10 mIU/mL) prevalence increased significantly from 27.9% in 1998 to 43.3% in 2010 (p<0.001). The national childhood HBV immunisation and catch-up programmes implemented in 1987 and 2001-2004, respectively, had a significant impact in reducing HBV infection and in raising the immunity of the adult population 18-29 years of age.
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Affiliation(s)
- Li Wei Ang
- Epidemiology & Disease Control Division, Ministry of Health, College of Medicine Building, 16 College Road, Singapore 169854, Singapore.
| | - Jeffery Cutter
- Communicable Diseases Division, Ministry of Health, College of Medicine Building, 16 College Road, Singapore 169854, Singapore
| | - Lyn James
- Epidemiology & Disease Control Division, Ministry of Health, College of Medicine Building, 16 College Road, Singapore 169854, Singapore
| | - Kee Tai Goh
- Communicable Diseases Division, Ministry of Health, College of Medicine Building, 16 College Road, Singapore 169854, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, MD3, 16 Medical Drive, Singapore 117597, Singapore
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Hepatitis B vaccination of adolescents: Significance of non-protective antibodies. Vaccine 2013; 32:62-8. [DOI: 10.1016/j.vaccine.2013.10.074] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Revised: 09/09/2013] [Accepted: 10/23/2013] [Indexed: 01/28/2023]
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