Immunization status and factors influencing hepatitis B vaccination of preterm infants in three provinces of China, 2019 to 2021.

BACKGROUND: Premature infants have less physiologic reserve and often delayed vaccination compared to full-term infants. The birth dose of hepatitis B vaccine (HepB-BD) is an essential measure to achieve the goal of "zero infections" of hepatitis B virus in all newborns. However, there are few investigations of hepatitis B vaccination of preterm infants, leading to uncertainty of coverage and insufficient knowledge of factors influencing timely vaccination of this important population. METHODS: We obtained hepatitis B vaccine (HepB) vaccination histories of premature infants born during 2019-2021 in three provinces from the respective provincial immunization information systems. Extracted data included date of birth, sex, region, and dates of HepB administration. We conducted descriptive analyses that included basic characteristics of the study subjects, HepB-BD administration, and full-series HepB vaccination. Factors potentially influencing HepB-BD and full series vaccination were analyzed by logistic regression. RESULTS: There were 1623 premature infants included in the analytic data set. Overall HepB-BD coverage was 71.41%; coverage among premature infants born to mothers with unknown hepatitis B surface antigen (HBsAg) status was 69.57%; coverage was higher at county-level-and-above hospitals (72.02%) than hospitals below county level (61.11%). Full-series HepB coverage was 94.15%; full-series coverage among preterm infants weighing less than 2000 g at birth was 76.92%. Logistic regression showed that the HepB-BD vaccination rate was positively associated with being born to an HBsAg-positive mother and being preterm with high birth weight. Regression analysis for factors influencing full-series HepB coverage showed that being born prematurely was positively associated with full-series coverage and being premature with a very low birth weight was negatively associated with full-series coverage. CONCLUSIONS: HepB-BD coverage levels in three provinces of China were less than the target of 90%, especially among premature infants born to mothers with unknown HBsAg status and at hospitals below the county level. Screening of pregnant women should be a universal normal standard. Hepatitis B vaccination training should be strengthened in hospitals to improve the HepB-BD vaccination rate of premature infants and to effectively prevent mother-to-child transmission of hepatitis B virus.

Hepatitis B virus infection and vaccination among people who use drugs in Xi'an, China.

BACKGROUND: While hepatitis B virus (HBV) infection in children has declined dramatically in China due to the vaccination strategy for newborns, HBV infection in high-risk adults is receiving an increasing attention. The number of people who use drugs (PWUD) in China is huge, but their status of HBV infection and vaccination is less reported, especially from large samples. The related knowledge can help decision makers develop the further strategy of HBV prevention and control. METHODS: A seroepidemiological survey was conducted in all four compulsory isolated detoxification centers (CIDCs) and all eight methadone maintenance treatment (MMT) clinics located in Xi'an, China. All PWUD who were undergoing detoxification or treatment in these settings were included. A questionnaire was designed to obtain the information of HBV vaccination history of participants, and sociodemographic and behavioral data of participants were obtained from the registration records of their respective CIDCs or MMT clinics. RESULTS: A total of 4705 PWUD participated in the survey. Positive rates of HBsAg (current infection) and HBsAg or anti-HBc (current/past infection) were 5.50% and 58.02%, notably higher than those reported for the general adult population in the same province during the same period. As age increased, the anti-HBc positive rate increased with statistically significant trend. The all-negative for HBsAg, anti-HBc, and anti-HBs accounted for 28.82%. Only 18.49% were identified by the questionnaire as having received HBV vaccine. The logistic regression found that compared with identified vaccinated PWUD, those unsure if having been vaccinated and those identified non-vaccinated had a significantly higher HBV current/past infection rate, with an increasing trend. CONCLUSION: PWUD are a high-risk adult group of HBV infection in China. Of them, more than half have not received HBV vaccine, and a significant portion are susceptible to HBV. Catch-up vaccination is need for this population to prevent and control HBV transmission.

Time interval distribution of hepatitis B vaccine immunization among infants in China from 2017 to 2021.

Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third doses is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from the Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28 and 61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61 and 214 days after the second dose 87,067 (64.1%) infants were vaccinated with the third dose between 151 and 180 days after the second dose. The time interval distribution varied across the four provinces or municipalities (p < .001). Of the 58,077 infants who completed the hepatitis B vaccine series, 36,377 (62.6%) infants used the same type of hepatitis B vaccine for all three doses. Overall, the timeliness of hepatitis B vaccination for infants was lower than expected, with regional disparities observed. This highlights the need for improved timeliness through the introduction of a defined timeframe for the last two doses of vaccine and training for obstetricians and related personnel.

Prevalence and factors associated with hepatitis B susceptibility among men who sex with men on HIV pre-exposure prophylaxis in Northeastern Brazil: a cross-sectional study.

BACKGROUND: This study aimed to determine the prevalence and factors associated with susceptibility to hepatitis B virus (HBV) among cisgender men who have sex with men (MSM) on HIV pre-exposure prophylaxis (PrEP) in Northeastern Brazil. METHODS: This was a cross-sectional, analytical study conducted between September 2021 and June 2023. Participants underwent structured interviews to collect sociodemographic and clinical information, including hepatitis B vaccination history, HIV PrEP use and sexual health history. Blood samples were collected for hepatitis B serologic testing: HBV surface antigen (HBsAg), HBV surface antibody (anti-HBs), total and IgM HBV core antibody (anti-HBc). HBV susceptibility was defined as nonreactive results for all these serological markers. RESULTS: A total of 287 participants were enrolled into the study. The median age of the individuals was 31 years (interquartile range: 27; 36). HBV susceptibility was found in 58 out 286 individuals (20.3%; 95% CI: 15.9-25.2). Seventy-six percent of the participants reported completing the three-dose hepatitis B vaccine schedule. Susceptibility was significantly associated with a monthly income ≤ 5 minimum wages (PR: 2.02; 95% CI: 1.01-4.05), lack of complete hepatitis B vaccination schedule (PR: 4.52; 95% CI: 2.89-7.06), initiation of HIV PrEP (PR: 2.18; 95% CI: 1.21-3.94), duration of six months of HIV PrEP (PR: 2.16; 95% CI: 1.19-3.91), absence of tattoos (PR: 1.55; 95% CI: 1.00-2.40) and no history of sexually transmitted infections (PR: 1.65; 95% CI: 1.07-2.54). CONCLUSION: Our findings highlight the significant burden of HBV susceptibility among MSM on HIV PrEP in Northeastern Brazil. Socioeconomic factors, vaccination status, PrEP use and sexual health behaviors play critical roles in determining susceptibility to HBV. Integrating hepatitis B screening and vaccination into PrEP services is critical for identifying and addressing HBV susceptibility among MSM. Interventions aimed at increasing vaccination coverage and promoting safer sexual practices are essential for mitigating the burden of HBV infection in this population.

Lymph node-targeted STING agonist nanovaccine against chronic HBV infection.

Chronic hepatitis B virus (HBV) infection is a global health problem that substantially increases the risk of developing liver disease. The development of a novel strategy to induce anti-HB seroconversion and achieve a long-lasting immune response against chronic HBV infection remains challenging. Here, we found that chronic HBV infection affected the signaling pathway involved in STING-mediated induction of host immune responses in dendritic cells (DCs) and then generated a lymph node-targeted nanovaccine that co-delivered hepatitis B surface antigen (HBsAg) and cyclic diguanylate monophosphate (c-di-GMP) (named the PP-SG nanovaccine). The feasibility and efficiency of the PP-SG nanovaccine for CHB treatment were evaluated in HBV-carrier mice. Serum samples were analyzed for HBsAg, anti-HBs, HBV DNA, and alanine aminotransferase levels, and liver samples were evaluated for HBV DNA and RNA and HBcAg, accompanied by an analysis of HBV-specific cellular and humoral immune responses during PP-SG nanovaccine treatment. The PP-SG nanovaccine increased antigen phagocytosis and DC maturation, efficiently and safely eliminated HBV, achieved a long-lasting immune response against HBV reinjection, and disrupted chronic HBV infection-induced immune tolerance, as characterized by the generation and multifunctionality of HBV-specific CD8+ T and CD4+ T cells and the downregulation of immune checkpoint molecules. HBV-carrier mice immunized with the PP-SG nanovaccine achieved partial anti-HBs seroconversion. The PP-SG nanovaccine can induce sufficient and persistent viral suppression and achieve anti-HBs seroconversion, rendering it a promising vaccine candidate for clinical chronic hepatitis B therapy.

An innate immune signature induced by AS01- or AS03-adjuvanted vaccines predicts the antibody response magnitude and quality consistently over time.

Background: Antibody-mediated protection can depend on mechanisms varying from neutralization to Fc-dependent innate immune-cell recruitment. Adjuvanted vaccine development relies on a holistic understanding of how adjuvants modulate the quantity/titer and quality of the antibody response. Methods: A Phase 2 trial (ClinicalTrials.gov: NCT00805389) evaluated hepatitis B vaccines formulated with licensed adjuvants (AS01B, AS01E, AS03, AS04 or Alum) in antigen-naïve adults. The trial investigated the role of adjuvants in shaping antibody-effector functions, and identified an innate transcriptional response shared by AS01B, AS01E and AS03. We integrated previously reported data on the innate response (gene expression, cytokine/C-reactive protein levels) and on quantitative/qualitative features of the mature antibody response (Fc-related parameters, immunoglobulin titers, avidity). Associations between the innate and humoral parameters were explored using systems vaccinology and a machine-learning framework. Results: A dichotomy in responses between AS01/AS03 and AS04/Alum (with the former two contributing most to the association with the humoral response) was observed across all timepoints of this longitudinal study. The consistent patterns over time suggested a similarity in the impacts of the two-dose immunization regimen, year-long interval, and non-adjuvanted antigenic challenge given one year later. An innate signature characterized by interferon pathway-related gene expression and secreted interferon-γ-induced protein 10 and C-reactive protein, which was shared by AS01 and AS03, consistently predicted both the qualitative antibody response features and the titers. The signature also predicted from the antibody response quality, the group of adjuvants from which the administered vaccine was derived. Conclusion: An innate signature induced by AS01- or AS03-adjuvanted vaccines predicts the antibody response magnitude and quality consistently over time.

Evaluation of interventions to improve timely hepatitis B birth dose vaccination among infants and maternal tetanus vaccination among pregnant women in Nigeria.

BACKGROUND: Nigeria has the largest number of children infected with hepatitis B virus (HBV) globally and has not yet achieved maternal and neonatal tetanus elimination. In Nigeria, maternal tetanus diphtheria (Td) vaccination is part of antenatal care and hepatitis B birth dose (HepB-BD) vaccination for newborns has been offered since 2004. We implemented interventions targeting healthcare workers (HCWs), community volunteers, and pregnant women attending antenatal care with the goal of improving timely (within 24 hours) HepB-BD vaccination among newborns and Td vaccination coverage among pregnant women. METHODS: We selected 80 public health facilities in Adamawa and Enugu states, with half intervention facilities and half control. Interventions included HCW and community volunteer trainings, engagement of pregnant women, and supportive supervision at facilities. Timely HepB-BD coverage and at least two doses of Td (Td2+) coverage were assessed at baseline before project implementation (January-June 2021) and at endline, one year after implementation (January-June 2022). We held focus group discussions at intervention facilities to discuss intervention strengths, challenges, and improvement opportunities. RESULTS: Compared to baseline, endline median vaccination coverage increased for timely HepB-BD from 2.6% to 61.8% and for Td2+ from 20.4% to 26.9% in intervention facilities (p < 0.05). In comparison, at endline in control facilities median vaccination coverage for timely HepB-BD was 7.9% (p < 0.0001) and Td2+ coverage was 22.2% (p = 0.14). Focus group discussions revealed that HCWs felt empowered to administer vaccination due to increased knowledge on hepatitis B and tetanus, pregnant women had increased knowledge that led to improved health seeking behaviors including Td vaccination, and transportation support was needed to reach those in far communities. CONCLUSION: Targeted interventions significantly increased timely HepB-BD and Td vaccination rates in intervention facilities. Continued support of these successful interventions could help Nigeria reach hepatitis B and maternal and neonatal tetanus elimination goals.

Modeling antigen-specific T cell dynamics following Hepatitis B Vaccination indicates differences between conventional and regulatory T cell dynamics.

Our study aims to investigate the dynamics of conventional memory T cells (Tconv) and regulatory memory T cells (Treg) following activation, and to explore potential differences between these two cell types. To achieve this, we developed advanced statistical mixed models based on mathematical models of ordinary differential equations (ODE), which allowed us to transform post-vaccination immunological processes into mathematical formulas. These models were applied to in-house data from a de novo Hepatitis B vaccination trial. By accounting for inter- and intra-individual variability, our models provided good fits for both antigen-specific Tconv and Treg cells, overcoming the challenge of studying these complex processes. Our modeling approach provided a deeper understanding of the immunological processes underlying T cell development after vaccination. Specifically, our analysis revealed several important findings regarding the dynamics of Tconv and Treg cells, as well as their relationship to seropositivity for Herpes Simplex Virus Type 1 (HSV-1) and Epstein-Barr Virus (EBV), and the dynamics of antibody response to vaccination. Firstly, our modeling indicated that Tconv dynamics suggest the existence of two T cell types, in contrast to Treg dynamics where only one T cell type is predicted. Secondly, we found that individuals who converted to a positive antibody response to the vaccine earlier had lower decay rates for both Tregs and Tconv cells, which may have important implications for the development of more effective vaccination strategies. Additionally, our modeling showed that HSV-1 seropositivity negatively influenced Tconv cell expansion after the second vaccination, while EBV seropositivity was associated with higher Treg expansion rates after vaccination. Overall, this study provides a critical foundation for understanding the dynamic processes underlying T cell development after vaccination.

Effect of hepatitis B vaccination on HBV-infection among school children in Yaounde; ten years after the introduction of HBV vaccine into routine Immunization Program in Cameroon.

Introduction: since the introduction of the anti-HBV vaccine into the Expanded Program on Immunization (EPI) in 2005 in Cameroon, vaccination coverage has reached 99.0%. This coverage would indicate an increase in the number of children immune to Hepatitis B Virus (HBV) and a decrease in susceptibility to HBV-infection. This study was conducted to evaluate the effect of the HBV vaccine on pediatric HBV-infection in Yaounde, Cameroon. Methods: this school-based cross-sectional study was conducted from February to May 2016 among 180 children from Nkomo public school. The study population was stratified into two groups: vaccinated (n=95) versus (vs) unvaccinated (n=85). Screening for HBV biomarkers was done using a rapid panel test for detection (HBsAg, HBeAg and anti-HBc) and anti-HBs titer using enzyme linked immunosorbent assay (ELISA). Statistical analyses were done using SPSS v. 22 with p < 0.05 considered significant. Results: the mean age was 9.65 years. HBsAg (p=0.019) and anti-HBc (p=0.001) rates were detected in children aged ≥10 years and children aged < 10 years (95.95% [71/74]) were vaccinated vs 22.64% (24/106) for those aged ≥10 years (OR: 80.86; 95% CI: 23.36%-279.87%, p < 0.0001). According to anti-HBV vaccination status, HBsAg rate varied from [9.41% (8/85) to 1.05% (1/95), p=0.025], HBeAg rate varied from [2.35% (2/85) to 0% (0/95), p= 0.42] and anti-HBc rate ranged from [12.94% (11/85) to 2.10% (2/95), p= 0.011]. Conclusion: despite the variability of the anti-HBs titer, vaccination against HBV has a positive effect on the reduction of HBV-infection in children in tropical settings such as Cameroon.

The Impact of Smoking on Long-Term Protection Following Hepatitis B Vaccination: A 24-Year Cohort Study.

The hepatitis B vaccination-induced immune response has been demonstrated to be associated with a number of factors, including age, sex, BMI, and the presence of comorbidities. Additionally, modifiable determinants such as smoking have been identified as influencing the response to vaccination. However, despite the evidence that smokers are at an increased risk of not responding to vaccination, the long-term effects of smoking on antibody persistence remain poorly understood. This study aims to assess the impact of smoking habits on long-term immunity following the primary vaccination cycle. Participants were required to have received a standard three-dose vaccine schedule in childhood, without subsequent doses, and to be between 18 and 24 years of age. Data on age, sex, BMI, age of administration of the first vaccine dose, and time between doses were collected. An antibody concentration < 10 IU/L was considered as non-protective. A total of 2133 individuals were included, 14.2% of whom were smokers. The mean age was 20.28 ± 0.92 years. The probability of having a non-protective antibody concentration was significantly higher in smokers than in non-smokers (AOR: 1.287; 95% CI: 1.002-1.652). The detrimental effects of smoking extend beyond the immediate effects on the vaccine response, also impairing the long-term immune response in individuals who received vaccinations during childhood.

Hepatitis B immunisation and immune status of nurses in a regional hospital in central South Africa.

BACKGROUND:  The hepatitis B virus (HBV) is one of the most important biological occupational hazards for healthcare workers. A high percentage of HBV infections are attributable to percutaneous occupational exposure. This study aimed to describe the HBV immunisation and current immune status of all the nurses employed in a regional hospital in central South Africa. METHODS:  A descriptive record review included all the nurses (N = 388) employed in a regional hospital in central South Africa from 01 January 2018 to 31 January 2020. A total of 289 health records were included in the study. Data were analysed using descriptive statistics. Logistic regression analysis was used to establish factors associated with full immunisation. RESULTS:  Most nurses were females (87.9%), working in medical (27.0%) wards. Only 20.4% of nurses received one dose of vaccine, while 51.2% received the three prescribed doses. However, 91.2% of nurses did not receive the vaccine at the correct intervals. Most of the tested nurses (71.0%) were immune. Immunisation status was significantly associated with religion (p  0.001) and schedule (p = 0.003). Nurses who were non-Christians were 35.9% less likely to be fully vaccinated compared to Christians. CONCLUSION:  Half of the nursing staff received three doses as prescribed. All nurses should receive the vaccine against HBV and their immune status monitored to minimise the risk of an infection. It is therefore recommended that proof of immunity should be a requirement.Contribution: This study found a high percentage of nurses with HBV antibodies, which will ensure workplace safety.

High Rates of Seroprotection to Hepatitis B After a Hepatitis B Challenge Dose in Previously Vaccinated Patients with Inflammatory Bowel Disease on Immunosuppressive Therapy.

BACKGROUND: Healthy populations have high rates of sustained vaccine-induced seroprotection to hepatitis B virus, but previous studies in immunosuppressed patients with inflammatory bowel disease (IBD) have shown suboptimal seroprotection rates. A challenge dose of hepatitis B vaccine (HepB) is recommended in previously vaccinated individuals who are seronegative to elicit an anamnestic response and determine if they are seroprotected. The aim of our study was to determine sustained seroprotection rates to hepatitis B vaccine (HepB) in patients with IBD. METHODS: This was a single-center prospective study of patients with IBD previously vaccinated with a three dose HepB series. Patients had a hepatitis B surface antibody (anti-HBs) drawn; if it was below 10 mIU/mL, they received a challenge dose of the HepB vaccine to assess for anamnestic response and sustained seroprotection. The primary outcome was to determine the rate of sustained seroprotection (anti-HBs ≥ 10). RESULTS: A total of 168 patients met inclusion criteria, mean age 35.7 years ± 13.6 standard deviation (SD). Initially 120 (71.4%) had anti-HBs ≥ 10 mIU/mL, with median anti-HBs of 37 mIU/mL (interquartile range 0-234); 48 (28.6%) needed a challenge dose, of which 34 responded with anti-HBs ≥ 10 mIU/mL. In total, 154 (91.7%) demonstrated sustained seroprotection to HepB. Those not seroprotected were more likely to have been vaccinated on immunosuppressive therapy or after their diagnosis of IBD. CONCLUSIONS: Most vaccinated patients with IBD maintain sustained seroprotection to HepB despite prolonged exposure to immunosuppression. This contradicts prior studies and shows that immunosuppression does not lead to loss of seroprotection.

HIV pre-exposure prophylaxis and opportunities for vaccination against hepatitis A virus, hepatitis B virus and human papillomavirus: an analysis of the Ontario PrEP cohort study.

OBJECTIVES: Populations who seek HIV pre-exposure prophylaxis (PrEP) are disproportionately affected by hepatitis A virus (HAV), hepatitis B virus (HBV) and human papillomavirus (HPV). We examined immunity/vaccination against these infections among participants in the Ontario PrEP cohort study (ON-PrEP). METHODS: ON-PrEP is a prospective cohort of HIV-negative PrEP users from 10 Ontario clinics. We descriptively analysed baseline immunity/vaccination against HAV (IgG reactive), HBV (hepatitis B surface antibody >10) and HPV (self-reported three-dose vaccination). We further performed multivariable logistic regression to identify characteristics associated with baseline immunity/vaccination. We used cumulative incidence functions to describe vaccine uptake among participants non-immune at baseline. RESULTS: Of 633 eligible participants, 59.1% were white, 85.8% were male and 79.6% were gay. We found baseline evidence of immunity/vaccination against HAV, HBV and HPV in 69.2%, 81.2% and 16.8% of PrEP-experienced participants and 58.9%, 70.3% and 10.4% of PrEP-naïve participants, respectively. Characteristics associated with baseline HAV immunity were greater PrEP duration (adjusted OR (aOR) 1.41/year, 95% CI 1.09 to 1.84), frequent sexually transmitted and bloodborne infection (STBBI) testing (aOR 2.38, 95% CI 1.15 to 4.92) and HBV immunity (aOR 3.53, 95% CI 2.09 to 5.98). Characteristics associated with baseline HBV immunity were living in Toronto (aOR 3.54, 95% CI 1.87 to 6.70) or Ottawa (aOR 2.76, 95% CI 1.41 to 5.40), self-identifying as racialised (aOR 2.23, 95% CI 1.19 to 4.18), greater PrEP duration (aOR 1.39/year, 95% CI 1.02 to 1.90) and HAV immunity (aOR 3.75, 95% CI 2.19 to 6.41). Characteristics associated with baseline HPV vaccination were being aged ≤26 years (aOR 9.28, 95% CI 2.11 to 40.77), annual income between CAD$60 000 and CAD$119 000 (aOR 3.42, 95% CI 1.40 to 8.34), frequent STBBI testing (aOR 7.00, 95% CI 1.38 to 35.46) and HAV immunity (aOR 6.96, 95% CI 2.00 to 24.25). Among those non-immune at baseline, overall cumulative probability of immunity/vaccination was 0.70, 0.60 and 0.53 among PrEP-experienced participants and 0.93, 0.80 and 0.70 among PrEP-naïve participants for HAV, HBV and HPV, respectively. CONCLUSIONS: Baseline immunity to HAV/HBV was common, and a sizeable proportion of non-immune participants were vaccinated during follow-up. However, HPV vaccination was uncommon. Continued efforts should be made to remove barriers to HPV vaccination such as cost, inclusion in clinical guidelines and provider recommendation.

Hepatitis B Virus Genotypes and Subgenotypes Circulating in Infected Residents in a Country with High Vaccination Rate.

Despite the availability of a vaccine against hepatitis B virus (HBV), this infection still causes public health problems, particularly in susceptible populations. In Portugal, universal free vaccination started in 1994, and most HBV infections are diagnosed in immigrants from high-prevalence countries. Our aim was to assess the pattern of HBV genotypes/subgenotypes in samples collected between 2017 and 2021 from a convenience sample of 70 infected residents in Portugal. The HBV pol/HBsAg region was amplified and sequenced, allowing the analysis of RT sequences submitted to phylogenetic analysis and mutations assessment. A total of 37.1% of samples were from native Portuguese, aged 25-53 years (mean: 36.7 years), and the remaining samples were from individuals born outside of Portugal. A high diversity of HBV was identified: subgenotypes A1-A3 in 41.0% (16/39); D1, D3, and D4 in 30.7% (12/39); E in 23.1% (9/39); and F4 in 2.6% (1/39). Besides genotypes A and D, Portuguese were also infected with genotypes E and F, which are prevalent in Africa and South America, respectively. Resistance mutations in RT sequences were not found. The findings provide valuable insights for updating the HBV molecular epidemiology in Portugal. However, successful strategies to prevent and control the infection are still needed in the country, especially among susceptible and vulnerable populations.

Serosusceptibility and hesitancy for booster HBV vaccination among health care workers in Italy: A cross-sectional study.

BACKGROUND: Health care workers (HCWs) are at increased risk of exposure to hepatitis B virus (HBV). The most effective prevention measure is vaccination, with a serum hepatitis B surface antibody (HBsAb) titre > 10 mIU/ml considered protective. To date, the sociodemographic and occupational characteristics related to HBV serosusceptibility and factors associated with booster hesitancy remain unclear. Therefore, this study aimed to identify factors associated with maintaining a protective HBsAb titre in a large sample of HCWs and to evaluate factors potentially associated with hesitancy towards vaccine boosters. METHODS: A cross-sectional study was conducted among HCWs who underwent a health surveillance visit between 2017 and 2022. If the serum HBsAb titre was < 10 MIU/ml, a vaccine booster dose was offered. Based on their willingness to be vaccinated, employees were classified into three groups: acceptance, hesitation, and refusal. Uni- and multivariable analyses were performed to assess the association of demographic and occupational characteristics with serosusceptibility and attitudes towards vaccination. RESULTS: A total of 1632 (27%) employees were shown to be nonimmune. A lower median age and being a physician were significantly associated with a protective HBsAb titre. A total of 706 nonimmune employees (43.3%) accepted the vaccination, 865 (53%) hesitated, and 61 (3.7%) refused. The median age of those who refused vaccination was significantly higher than that of those who hesitated and those who were vaccinated. Acceptance of vaccination was significantly higher among nurses, while nurse aides hesitated more; among nonmedical graduate staff both hesitation and refusal were higher than expected. In the multivariable analysis, higher age, female sex, and employment as an allied health care professional were shown to be significantly associated with hesitation/refusal, while being born abroad turned out to be protective. CONCLUSIONS: Our study showed that approximately a quarter of HCWs were not immune to HBV infection, and of these, more than half were hesitant towards or refused the booster dose. The risk of hesitation/refusal was higher with age in women and among allied health care staff. Based on these findings, further studies are needed to prospectively evaluate HBV seroprevalence, vaccination adherence, factors associated with hesitancy, and the effectiveness of health surveillance strategies in a high-risk population susceptible to infection.

High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response.

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.

Experimental and molecular dynamics simulation studies on the physical properties of three HBc-VLP derivatives as nanoparticle protein vaccine candidates.

Self-assembling virus-like particles (VLPs) are promising platforms for vaccine development. However, the unpredictability of the physical properties, such as self-assembly capability, hydrophobicity, and overall stability in engineered protein particles fused with antigens, presents substantial challenges in their downstream processing. We envision that these challenges can be addressed by combining more precise computer-aided molecular dynamics (MD) simulations with experimental studies on the modified products, with more to-date forcefield descriptions and larger models closely resembling real assemblies, realized by rapid advancement in computing technology. In this study, three chimeric designs based on the hepatitis B core (HBc) protein as model vaccine candidates were constructed to study and compare the influence of inserted epitopes as well as insertion strategy on HBc modifications. Large partial VLP models containing 17 chains for the HBc chimeric model vaccines were constructed based on the wild-type (wt) HBc assembly template. The findings from our simulation analysis have demonstrated good consistency with experimental results, pertaining to the surface hydrophobicity and overall stability of the chimeric vaccine candidates. Furthermore, the different impact of foreign antigen insertions on the HBc scaffold was investigated through simulations. It was found that separately inserting two epitopes into the HBc platform at the N-terminal and the major immunogenic regions (MIR) yields better results compared to a serial insertion at MIR in terms of protein structural stability. This study substantiates that an MD-guided design approach can facilitate vaccine development and improve its manufacturing efficiency by predicting products with extreme surface hydrophobicity or structural instability.

Disparate kinetics in immune response of two different Haemophilus influenzae type b conjugate vaccines: Immunogenicity and safety observations from a randomized controlled phase IV study in healthy infants and toddlers using a 2+1 schedule.

Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.

Vaccination against Haemophilus influenzae type b (Hib) is included in the majority of national immunization programs worldwide and has shown to be effective in preventing Hib disease. In Europe, different vaccines containing Hib components are marketed. We compared the immune response and safety of 2 of these (DTPa-HBV-IPV/Hib, Ih group) and DTaP5-HB-IPV-Hib, Va group) in infants and toddlers, when used in a 2 + 1 schedule, i.e. two primary vaccination doses (at 2 and 4 months of age of the infant), followed by one booster dose at the age of one year. One month after the booster vaccination, the antibody concentration ratio between both groups (Ih group/Va group) was 0.917 (95% CI: 0.710­1.185) showing the DTPa-HBV-IPV/Hib vaccine was non-inferior to the DTaP5-HB-IPV-Hib vaccine; the difference in percentage of participants (Ih group ­ Va group) with antibody concentrations above 5 µg/mL was -6.3% (95% CI: −14.1% to 1.5%), which did not meet the pre-defined criterion for non-inferiority. In the Ih group, the quality of antibodies produced was somewhat higher versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. The kinetics of the immune response are different between the 2 vaccines. Since both vaccines contain different additional components (conjugated proteins), a possible effect of concomitant (simultaneously administered) vaccines was studied. Further investigations to confirm our findings are needed.

Comparison of the effectiveness four years after Homo/Hetero prime-boost with 10 µg HP and 20 µg CHO recombinant hepatitis B vaccine at 1 and 6 months in maternal HBsAg-negative children.

Introduction: Limited data were available on the effectivenessfour years after Homo or Hetero prime-boost with 10 µg Hansenulapolymorpha recombinant hepatitis B vaccine (HepB-HP) and 20 µgChinese hamster ovary cell HepB (HepB-CHO). Methods: A crosssectional study was performed in maternalhepatitis B surface antigen (HBsAg)-negative children whoreceived one dose of 10 µg HepB-HP at birth, Homo or Heteroprime-boost with 10 µg HepB-HP and 20 µg HepB-CHO at 1 and 6months. HBsAg and hepatitis B surface antibody (anti-HBs) fouryears after immunization were quantitatively detected by achemiluminescent microparticle immunoassay (CMIA). Results: A total of 359 children were included; 119 childrenreceived two doses of 10 µg HepB-HP and 120 children receivedtwo doses of 20 µg HepB-CHO, called Homo prime-boost; 120children received Hetero prime-boost with 10 µg HepB-HP and 20µg HepB-CHO. All children were HBsAg negative. The geometricmean concentration (GMC) and overall seropositivity rate (SPR) ofanti-HBs were 59.47 (95%CI: 49.00 - 72.16) mIU/ml and 85.51%(307/359). Nearly 15% of the study subjects had an anti-HBsconcentration < 10 mIU/ml and 5.01% had an anti-HBsconcentration ≤ 2.5 mIU/ml. The GMC of the 20 µg CHO Homoprime-boost group [76.05 (95%CI: 54.97 - 105.19) mIU/ml] washigher than that of the 10 µg HP Homo group [45.86 (95%CI:31.94 - 65.84) mIU/ml] (p = 0.035). The GMCs of the Heteroprime-boost groups (10 µg HP-20 µg CHO and 20 µg CHO-10 µgHP) were 75.86 (95% CI: 48.98 - 107.15) mIU/ml and 43.65(95%CI: 27.54 - 69.18) mIU/ml, respectively (p = 0.041). Aftercontrolling for sex influence, the SPR of the 20 µg CHO Homoprime-boost group was 2.087 times than that of the 10 µg HPHomo group. Discussion: The HepB booster was not necessary in the generalchildren, Homo/Hetero prime-boost with 20 µg HepB-CHO wouldincrease the anti-HBs concentration four years after immunization,timely testing and improved knowledge about the self-pay vaccinewould be good for controlling hepatitis B.