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To evaluate the long-term efficacy and anamnestic response of Chinese hamster ovary (CHO) cell-derived hepatitis B vaccine (CHO-HepB) after 18-20 years, a cross-sectional survey was conducted in seven communities in Zhengding County at the end of 2017. The birth cohort 1997-1999 vaccinated primarily with three doses of CHO-HepB were enrolled in the survey. The HBV serological markers were quantified using the Chemiluminescence method. The infection status of HBsAg-positive participants was determined by comparing their results with the previous data. For those with an anti-HBs antibody negative, the anamnestic response was evaluated by measuring anti-HBs antibody concentrations following a dose of HepB administration. A total of 1352 participants were enrolled, with the prevalence of HBsAg, anti-HBs, and anti-HBc being 0.4 %, 74.5 %, and 1.3 %, respectively. There was no significant difference in the HBV markers (HBsAg, anti-HBs and anti-HBc) between birth-year groups (P > 0.05). The geometric mean concentration (GMC) of anti-HBs antibodies among 1007 positive participants was 191 mIU/ml. No new infections or carriers were identified in the survey. Combined with the three previous surveys of the same birth cohort, the positive rates of HBsAg, anti-HBs, and anti-HBc remained largely unchanged over two decades following CHO-HepB vaccination. Of 248 participants who received a booster vaccination, 231 (93.1 %) showed an anti-HBs antibody positive with a GMC of 369 mIU/mL. Moreover, the positive rate and GMC of anti-HBs were higher in the CHO-HepB booster group compared to the Saccharomyces cerevisiae-HepB booster group. The long-term efficacy of the CHO-HepB remains stable for 18-20 years after primary vaccination, and a higher seroconversion rate of anti-HBs is observed following a booster vaccination of CHO-HepB. Given the absence of new infections or carriers over the past two decades, it appears unnecessary to administer a booster vaccination of HepB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Heplisav-B, a CpG-adjuvanted recombinant hepatitis B virus (HBV) vaccine, has a higher seroprotection rate and immunogenicity than the conventional HBV vaccine. This study aimed to identify the predictors of HBV seroprotection post-transplantation in thoracic organ transplant recipients who received Heplisav-B., Methods: We conducted a retrospective study of adult thoracic organ (heart and lung) transplant recipients at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2020 and August 2023. Patients who completed Heplisav-B series were classified into three strategies: strategy A (completed 2 doses of Heplisav-B pre-transplantation with achieved seroprotection pre-transplantation), strategy B (received first dose of Heplisav-B pre-transplantation and second dose of Heplisav-B post-transplantation), and strategy C (completed 2 doses of Heplisav-B post-transplantation). HBV seroprotection was defined as HBsAb ≥10 IU/L., Results: A total of 154 thoracic organ transplant recipients completed Heplisav-B vaccine series. Post-transplant seroprotection was highest in strategy A, followed by strategy B and strategy C (54/76 [71 %] vs. 18/39 [46 %] vs. 14/39 [36 %]; p < 0.001). Multivariate logistic regression analysis identified two independent factors predicting lack of HBV seroprotection post-transplantation; both were related to Heplisav-B schedule: strategy B (adjusted odds ratio [aOR], 2.482; 95 % confidence interval [CI] 1.085 5.679; p = 0.031), and strategy C (aOR 4.963; 95 % CI 2.106 11.697; p < 0.001)., Conclusion: The vaccine schedule significantly predicts HBV seroprotection in adult thoracic organ transplant recipients. Our data supports the recommendation that pre-transplantation Heplisav-B to achieve HBsAb ≥10 IU/L is the optimal vaccination schedule to maintain an HBsAb level of ≥10 IU/L post-transplantation. Further studies are needed to determine whether this observation can be replicated in non-thoracic organ transplant recipients or pediatric populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background and Objectives: Hepatitis B vaccination (HBV) requires 6 months to complete and is recommended for patients with multiple sclerosis (PWMS), particularly those who are candidates for anti-CD20 therapy. However, limited data exist on HBV immunogenicity in PWMS receiving disease-modifying therapies (DMTs) and the impact of starting anti-CD20 therapy during immunization. We aimed to evaluate HBV immunogenicity in PWMS starting anti-CD20 therapy during vaccination, focusing on the number of doses received before anti-CD20 initiation., Methods: We conducted a retrospective analysis of a prospective cohort of adult PWMS at a single center in Spain, from April 2015 to May 2023. Eligible participants completed a 4-dose HBV course and underwent postvaccination serologic testing. We assess seroprotection rates (SRs), defined as the percentage of patients achieving anti-hepatitis B surface antibody titers ≥10 IU/L, focusing on those who switched to anti-CD20 therapy during vaccination, based on doses received before starting anti-CD20 and type of DMT at vaccination start. A multivariate generalized linear model (GLM) was used to identify factors associated with higher seroconversion., Results: A total of 289 PWMS (median [interquartile range (IQR)] age, 47.7 [42.8-54.4] years; 65.7% female; median [IQR] disease duration, 14.8 [6.7-21.2] years) were included. SRs progressively declined with fewer doses before anti-CD20 initiation, from 92.8% (95% CI 87.1-96.5) for 4 doses to 24.0% (95% CI 9.4-45.1) for 1 dose. Patients transitioning from sphingosine 1-phosphate (S1P) modulators showed the lowest SR at 25.0% (95% CI 7.3-52.4). The multivariate GLM confirmed these findings, with 3 doses (SR ratio 3.23 [95% CI 1.68-6.23]; p = 0.0005) or 4 doses (SR ratio 3.76 [95% CI 1.96-7.24]; p < 0.0001) before anti-CD20 therapy significantly associated with higher SRs, while starting S1P modulators at vaccination onset was significantly associated with lower SRs (SR ratio 0.42 [95% CI 0.23-0.78]; p = 0.0058). Female sex (SR ratio 1.15 [95% CI 1.01-1.32]; p = 0.0389) and younger age (SR ratio 0.90 [95% CI 0.83-0.97]; p = 0.0036) were also significantly associated with higher SRs., Discussion: Initiating anti-CD20 therapy during HBV negatively affects SRs, with a direct correlation with the number of doses received before anti-CD20 initiation. Early planning and execution of required vaccinations are crucial in managing PWMS., Classification of Evidence: This study provides Class III evidence that HBV during initiation of anti-CD20 therapy is less effective in establishing seroprotection to hepatitis B than in patients in whom HBV is completed before initiation of anti-CD20 therapy.

Dendritic cells are the most potent antigen-presenting cells in immune therapeutic approaches for chronic hepatitis B (CHB) infection. Here, we developed a clinical trial to evaluate the efficacy and safety of autologous HBV vaccine-pulsed DCs and their induced T cells (HPDCT) in CHB patients. This was a randomised, prospective, open-label, multicentre, superiority study and 309 treatment-naive CHB patients were divided into HPDCT plus nucleos(t)ide analogues (NAs) group (n = 84), NAs mono-therapy group (n = 82), HPDCT plus Peg-interferon (Peg-IFN) group (n = 69), Peg-IFN mono-therapy group (n = 74). Twelve times of HPDCT vaccinations were given intravenously, and all the patients were followed up for 72 weeks. In total, 1836 HPDCT infusions were administered with no obvious toxicity and side effect although few patients had self-limited low fever. More patients got HBsAg loss in those receiving HPDCT therapy. Patients of HPDCT plus Peg-IFN group with HBV DNA < 1 × 10 7  IU/mL at baseline exhibited earlier, stronger and longer lasting of viral response, especially HBV DNA < 20 IU/mL, than those patients of Peg-IFN mono-therapy group, from week 24 till week 72 (p < 0.05). Comparable efficacy was observed between the patients of HPDCT plus NAs group and NAs mono-therapy groups. In addition, CD25 on CD8 + T cells and HBV-specific CD8 + T cell increased significantly in patients of HPDCT combined antiviral drugs therapy. HPDCT combined with antiviral drugs was safe and able to enhance T cell immunity. Furthermore, HPDCT combined with Peg-IFN could provide an incremental benefit to patients with baseline levels of lower HBV DNA. Trial Registration: ClinicalTrials.gov identifier: NCT01935635., (© 2025 John Wiley & Sons Ltd.)

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., (© 2025 John Wiley & Sons Ltd.)

The nature of vaccine response inferiority is not well studied in children living with HIV (CLHIV). The authors investigated Hepatitis B Virus (HBV) and Diphtheria/Pertussis/Tetanus toxoid (DPT) vaccination responses following primary immunization in CLHIV (n = 42) and healthy controls (HC) (n = 38) and the effect of an additional vaccine dose. Antibody responses, CD4 and HBV-specific T/B cells were analysed using CMIA/ELISA and flow-cytometry. CLHIV had significantly lower baseline median antibody titres for all vaccines than HC (p <0.02). Differential seroprotection rates observed in CLHIV were, 4.8% for pertussis; 9.5% for HBV; 26.2% for diphtheria and 66.7% for tetanus. WHO staging significantly influenced anti-HBs levels (p = 0.0095). HBsAg-specific CD4+T-cells were significantly higher in CLHIV than HC (p = 0.042). An additional vaccine dose (HBV and Tdap) conferred a higher protection rate for tetanus and diphtheria (p <0.040) in CLHIV. These findings suggest that CLHIV exhibit a hierarchy of vaccine responses affecting antibody levels and protection rate, which was rescued by administering additional vaccine dose., Competing Interests: Declarations. Conflict of Interest: None., (© 2024. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Importance: Nonresponse to hepatitis B vaccine is common among people with HIV, resulting in vulnerability to infection with hepatitis B virus (HBV)., Objective: To compare the seroprotection response achieved with a 2-dose (noninferiority, 10% margin) and a 3-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine) vs a conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine) in people with HIV and prior nonresponse to HepB-alum vaccine., Design, Setting, and Participants: This phase 3, open-label, randomized clinical trial included people with HIV receiving antiretroviral therapy (CD4 cell count ≥100 cells/μL and HIV RNA <1000 copies/mL) without past or present serological evidence of having HBV or a response to hepatitis B vaccine. From December 2020 to February 2023, 561 adults were enrolled in the study at 41 sites in 10 countries in Africa, Asia, North America, and South America with follow-up for the primary outcome analysis through September 4, 2023., Interventions: Participants were randomly assigned to receive 2 doses of HepB-CpG vaccine administered intramuscularly at weeks 0 and 4; 3 doses of HepB-CpG vaccine administered intramuscularly at weeks 0, 4, and 24; or 3 doses of HepB-alum vaccine administered intramuscularly at weeks 0, 4, and 24., Main Outcomes and Measures: The primary outcome was a seroprotection response to hepatitis B vaccine (defined as level of antibody titer against hepatitis B surface antigen [HBsAg] ≥10 mIU/mL) at week 12 for the 2-dose regimen (8 weeks after dose 2) and at week 28 for 3-dose regimens (4 weeks after dose 3). Key secondary outcomes included seroprotection response at additional time points, antibody titer against HBsAg, and adverse events within 4 weeks of hepatitis B vaccination., Results: Of 561 participants included in the analysis (median age, 46 years [IQR, 31-56 years]); 64% were male; 17% of participants were Asian, 42% were Black, and 35% were White), a seroprotection response was achieved in 93.1% who received 2 doses of HepB-CpG vaccine (n = 174), in 99.4% who received 3 doses of HepB-CpG vaccine (n = 169), and in 80.6% who received 3 doses of HepB-alum vaccine (n = 165). The stratified difference in seroprotection response between the 2-dose HepB-CpG vaccine group and the 3-dose HepB-alum vaccine group was 12.5% (97.5% CI, 4.1%-20.9%), achieving noninferiority and indicating superiority. The 3-dose HepB-CpG vaccine regimen was superior to the 3-dose HepB-alum vaccine regimen (stratified difference in seroprotection response, 18.4% [repeated 97.5% CI, 10.4%-26.2%]). By week 12, more than 90% of participants who received HepB-CpG vaccine achieved a seroprotection response. The 3-dose regimen of HepB-CpG vaccine achieved a higher proportion of participants with antibody titer against HBsAg greater than 1000 mIU/mL (78.1%) vs the other 2 regimen groups (26.4% for 2 doses of HepB-CpG vaccine and 35.2% for 3 doses of HepB-alum vaccine). No unexpected safety issues were observed., Conclusions and Relevance: Among people with HIV and nonresponse to prior hepatitis B vaccination, both the 2-dose and 3-dose regimens of HepB-CpG vaccine achieved a superior seroprotection response compared with 3 doses of HepB-alum vaccine., Trial Registration: ClinicalTrials.gov Identifier: NCT04193189.

Background: Kyrgyzstan introduced universal hepatitis B childhood vaccination in 1999 to reduce the burden of hepatitis B. In 2016, aligned with the goal of controlling hepatitis B in the WHO European Region, a regional target of 0.5% was set for seroprevalence of hepatitis B surface antigen (HBsAg) among targeted birth cohorts. We conducted a representative nationwide serosurvey to assess the HBsAg prevalence among third-grade school children in Kyrgyzstan in 2022., Methods: We sampled numbers of children proportional to the population size and stratified the sample by region and urbanization level (urban/rural). We applied multistage cluster sampling with school classes as clusters. Identified participants in the survey were tested for HBsAg, using Enzyme-linked Immunosorbent Assay (ELISA), and positive samples confirmed with neutralization tests. Data on vaccination coverage for hepatitis B birth dose (HepB BD), including timing, and three doses of hepatitis B vaccine (HepB3) were collected from medical vaccination records. We calculated crude and weighted proportions for HBsAg seroprevalence and HepB BD and HepB3 coverage., Results: From the target sample size of 3,352 children, a total of 3,183 children (95%) participated in the survey. The majority of children were 9 or 10 years old (2,964; 93%) with almost equal numbers of girls and boys (1,606; 50% boys) and rural and urban participants (1,624; 51% urban). Five participants tested positive for HBsAg in confirmatory tests. The weighted HBsAg seroprevalence was 0.12% (95% CI 0.04-0.35%). Weighted coverage for HepB BD was 88% (95% CI 86-90%) and for HepB3 90% (95% CI 86-93%). Results from crude and weighted analysis did not differ statistically., Conclusions: Our study demonstrates the impact of a successfully implemented hepatitis B vaccination programme in Kyrgyzstan. High hepatitis B vaccination coverage has resulted in very low HBsAg seroprevalence among vaccinated birth cohorts, paving the way towards the achievement of regional hepatitis B control targets. Maintaining high vaccination uptake plus additional measures like screening of pregnant women and treatment of those infected will be key to achieve elimination of vertical transmission of hepatitis B in Kyrgyzstan., Competing Interests: Declarations. Ethics approval and consent to participate: The protocol of this study has been evaluated by the Ethical Committee of the MoH and given a positive vote on 9 August 2021. Written informed consent was obtained from parents or legal guardians of all children participating in the current study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This study aimed to evaluate the impact of Thailand's hepatitis B virus (HBV) National Program Immunization (NPI), 32 years post-implementation, on infection rates and immunity in various age groups. A cross-sectional study involved 6,068 participants aged 6 months to 80 years from four regions in Thailand. Blood samples were tested for HBsAg, anti-HBs, and anti-HBc using a chemiluminescent immunoassay. Data were compared across age groups and with previous surveys from 2004 to 2014. Individuals born after the implementation of the NPI had significantly lower HBV infection rates (p < 0.0001). No HBsAg was detected in individuals under 20 years old. The prevalence of HBV carriers increased with age, from 0.3% in the 21-30 group to 4.3% in those over 60, with an overall prevalence of 1.7%. Percentages of seroprotected individuals (anti-HBs ≥ 10 mIU/mL) were high in young children but dropped to 19.4% in ages 11-20 and 12.5% in ages 21-30. Anti-HBc was found at very low rates in children but increased significantly after age 30. Thailand's HBV NPI significantly reduced HBV infection rates, especially in younger populations. This study highlighted the program's success and guided future elimination efforts to achieve hepatitis elimination goal by 2030., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

PreHevbrio® is a 3-antigen HBV vaccine (3-A-HBV) engineered to express the three HBV envelope proteins; the small 'S' hepatitis B surface antigen (SHBs or HBsAg), the middle pre-S2 + HBsAg (MHBs) and the large PreS1 + PreS2 + HBsAg (LHBs) antigens. 3-A-HBV has been shown to induce superior and more durable antibody responses relative to a 1-A-HBV despite containing half the 'S' antigen dose. To explain the mechanism(s) behind the high immunogenicity, the potential influence of mammalian glycosylation, HBs antigen conformation, anti-HBs epitope binding profiles and T-cell responses to the PreS antigens were investigated. In this paper, we demonstrate that glycosylation status does not play a role in the increased immunogenicity of the 3-A-HBV, but that the 3-A-HBV particles are able to induce T cell responses to PreS1 and PreS2 antigens. Epitope mapping demonstrated that the 3-A-HBV particles are inherently more antigenic than 1-A-HBV particles, leading to quantitative differences in the anti-HBs antibody response. Further, we demonstrate that the T cell responses significantly correlate with the higher observed anti-HBs titers and may contribute to the higher and more durable anti-HBs titers. This trial is registered at Clinicaltrials.gov (NCT03393754) and EudraCT (2017-001819-36)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David E Anderson reports financial support was provided by VBI Vaccines Inc. David E Anderson reports a relationship with VBI Vaccines Inc. that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Illia Petrov reports statistical analysis was provided by VBI Vaccines Inc. Illia Petrov reports a relationship with VBI Vaccines Inc. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Barthelemy Ontsouka reports financial support was provided by VBI Vaccines Inc. Barthelemy Ontsouka reports a relationship with VBI Vaccines Inc. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Catalina Soare reports financial support was provided by VBI Vaccines Inc. Catalina Soare reports a relationship with VBI Vaccines Inc. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Daniel Plaskin reports financial support was provided by VBI Vaccines Inc. Daniel Plaskin reports a relationship with VBI Vaccines Inc. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Lanjian Yang reports financial support was provided by VBI Vaccines Inc. Lanjian Yang reports a relationship with VBI Vaccines Inc. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Rachel Hammond reports a relationship with Clear B Therapeutics that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Tamara Berthoud reports financial support was provided by VBI Vaccines Inc. Tamara Berthoud reports a relationship with VBI Vaccines Inc. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Tanvir Ahmed reports financial support was provided by VBI Vaccines Inc. Tanvir Ahmed reports a relationship with VBI Vaccines Inc. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Francisco Diaz-Mitoma reports a relationship with VBI Vaccines, Inc. that includes: consulting services and equity stocks. If there are other authors, they declare that they have no known competing financial interest or personal relationships that could have appeared to influence the the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Childhood cancer treatment disrupts vaccination schedules and weakens or eliminates vaccine-induced immunity. In addition, post-treatment vaccine responses vary. This study aimed to assess post-treatment serum antibody levels and vaccine responses in children., Methods: Pediatric patients treated at Hacettepe University between years 2015 and 2020, achieved remission after chemotherapy for lymphoma and solid tumors were included. Post-treatment vaccination status, serum antibody levels for hepatitis A (HAV), hepatitis B (HBV), varicella-zoster (VZV), measles-mumps-rubella (MMR), and changes in vaccine responses were retrospectively analyzed., Results: The study included 533 patients. Post-treatment seronegativity rates were: measles (83.5%), HAV (64%), rubella (60.1%), HBV (48.5%), VZV (43.3%), and mumps (28%). Post-treatment antibody loss was observed for measles (47.1%), HAV (31.9%), HBV (31.4%), mumps (28.6%), VZV (21.7%), and rubella (11.4%). Seropositivity after 1 vaccine dose was seen with HAV (83.6%), rubella (82.9%), HBV (81.4%), VZV (63.5%), mumps (45.4%), and measles (33.3%). Seropositivity after 2 vaccine doses was achieved with HAV (98.8%), VZV (84.6%), rubella (80%), HBV (80%), measles (32.2%), and mumps (36.2%)., Conclusion: Post-treatment serological vaccine responses in children were lower than anticipated despite multiple doses. Given the potential need for periodic serological assessments and booster vaccinations, long-term follow-ups are planned., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)