HepB Vaccine Research Articles

EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients

According to a recent World Health Organization estimate, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which originated in China in 2019, has spread globally, infecting nearly 100 million people worldwide by January 2021. Patients with chronic liver diseases (CLD), particularly cirrhosis, hepatobiliary malignancies, candidates for liver transplantation, and immunosuppressed individuals after liver transplantation appear to be at increased risk of infections in general, which in turn translates into increased mortality. This is also the case for SARS-CoV-2 infection, where patients with cirrhosis, in particular, are at high risk of a severe COVID-19 course. Therefore, vaccination against various pathogens including SARS-CoV-2, administered as early as possible in patients with CLD, is an important protective measure. However, due to impaired immune responses in these patients, the immediate and long-term protective response through immunisation may be incomplete. The current SARS-CoV-2 pandemic has led to the exceptionally fast development of several vaccine candidates. A small number of these SARS-CoV-2 vaccine candidates have already undergone phase III, placebo-controlled, clinical trials in healthy individuals with proof of short-term safety, immunogenicity and efficacy. However, although regulatory agencies in the US and Europe have already approved some of these vaccines for clinical use, information on immunogenicity, duration of protection and long-term safety in patients with CLD, cirrhosis, hepatobiliary cancer and liver transplant recipients has yet to be generated. This review summarises the data on vaccine safety, immunogenicity, and efficacy in this patient population in general and discusses the implications of this knowledge on the introduction of the new SARS-CoV-2 vaccines.

Evolution between 2008 and 2018 of mothers’ perception regarding vaccination and infant vaccine coverage in France

ObjectiveMonitoring of vaccination coverage rates (VCRs) is essential to assess the implementation of a country's vaccine policy and its effectiveness. Through the French Vaccinoscopy study, we measured the evolution of VCRs as well as mothers’ opinion towards vaccination between 2008 and 2018, before and after implementation of infant mandatory vaccination extension. MethodsThis is a study based on an internet-standardised questionnaire. In 2018, a representative sample of 3000 mothers of infants 0 to 35 months of age answered on their opinion on vaccination and reported all vaccinations recorded in their child's health record. ResultsOn the period considered, infant VCRs were stable and high for diphtheria, tetanus, poliomyelitis, pertussis and pneumococcus components and progressed for measles, mumps rubella, 2 doses at 24 months of age from 45.3% in 2008 to 81.0% in 2018, hepatitis B (HepB) complete primovaccination at 6 months of age from 45.9% in 2008 to 86.3% in 2017 and 95.5% in 2018, and meningococcus C (MenC) 1 dose at 6 months of age from 43.0% in 2017 to 74.2% in 2018. In 2018, 69.0% of mothers were in favour of vaccination while this rate dropped from 80.2% in 2012 to 64.0% in 2017, and 80.8 to 89.6% perceived HepB, MenC measles and pertussis vaccinations as useful/essential, percentages in progress versus 2017. ConclusionFollowing the implementation of infant mandatory vaccination in 2018, proportion of mothers in favour of vaccination increased significantly. HepB and MenC VCRs significantly progressed between 2017 and 2018.

1055. Assessing the Impact of the Routine Childhood Hepatitis B Immunization and the Need for Hepatitis B Vaccine Birth Dose in Sierra Leone, 2018

BackgroundAll African countries recommend 3 doses of hepatitis B vaccine (HepB3), most at 6, 10, and 14 weeks of age, but few recommend a HepB birth dose (HepB-BD). To evaluate the role of mother to child transmission (MTCT) of hepatitis B virus (HBV) with the 3 dose HepB schedule, we conducted a serosurvey in Sierra Leone among 4–30 month old children and their mothers, and 5–9 year old children.MethodsWe conducted a multi-stage cluster survey in 3 districts. Enumeration areas (EA) were selected by probability proportional to size, followed by random selection of eligible households to identify 1901 children per age group. We tested all participants for HBV surface antigen (HBsAg) by rapid test and collected children’s HepB vaccination history. Serum from all HBsAg+ mothers and 1 HBsAg- mother per EA was tested for total antibodies to HBV core antigen (anti-HBc), HBsAg, HBV e antigen (HBeAg), and HBV DNA. We assessed the association of HBsAg prevalence with HepB vaccination and maternal HBV markers.ResultsAmong 1889 children aged 4–30 months, 20 (1.3%; 95% CI:0.8%–2.0%) were HBsAg+; HepB3 coverage was 85%. Among 2025 children aged 5–9 years, 32 (1.6%; 95% CI:1.1%–2.3%) were HBsAg+; HepB3 coverage was 77%. Of HBsAg+ children, 70% (14/20) of younger and 56% (18/32) of older children received HepB3. Among 1776 mothers of younger children, 169 (9.8%; 95% CI:8.1%–11.7%) were HBsAg+. HBsAg prevalence for children with HBsAg+ mothers was 5.9% (10/169) and 0.7% (6/1605) for those with HBsAg- mothers (adjusted OR=10.6 [95% CI:2.8–40.8]). Of 139 HBsAg+ mothers, 13 (9%) were HBeAg+ and 126 (91%) had detectable HBV DNA. Maternal HBsAg (p=0.026), HBeAg (p< 0.001), and HBV DNA levels ≥ 200,000 IU/mL (p< 0.001) were associated with HBsAg positivity in younger children (Table 1).Table 1: Association of maternal HBV serological and molecular markers with HBsAg positivity in 4–30-month old children — Sierra Leone hepatitis B serosurvey, 2018 ConclusionHBsAg prevalence was much lower among children than among mothers, for whom HepB would not have been available, indicating that routine infant HepB vaccination has substantially lowered HBV burden. Increasing HepB3 coverage could further reduce HBsAg prevalence among children. As HBsAg positivity in young children was strongly associated with having a mother with active HBV infection and > 50% of HBsAg+ children received HepB3, HepB-BD is needed to prevent MTCT of HBV and chronic HBV infections in children.Disclosures All Authors: No reported disclosures

1393. Factors Associated with Co-administration of Pentavalent DTaP-IPV/Hib and Monovalent Hepatitis B Vaccine in the United States (US)

BackgroundThe US vaccination schedule includes DTaP, IPV, Hib and HepB doses in the first 6 months of life. A previous analysis found variability in the timing of HepB doses in infants receiving DTaP-IPV/Hib. We explored factors associated with co-administration of DTaP-IPV/Hib and HepB on the same day.MethodsThis was a retrospective study using the MarketScan® commercial claims and encounters database. Infants born from 1 July 2010 - 30 June 2016, continuously enrolled in an insurance plan for ≥ 13 months and receiving ≥ 3 DTaP-IPV/Hib doses were included.Infants were assessed for HepB claims relative to the first and third DTaP-IPV/Hib doses. Because a HepB birth dose was assumed, the first HepB claim from 29 - 169 days following birth was counted as Dose 2, and the second claim from 170 days - 12 months as Dose 3. Associations between demographic, provider, and insurance characteristics, receipt of other pediatric vaccines, and co-administration of DTaP-IPV/Hib and HepB were analyzed using multivariate logistic regression.ResultsAmong 165,553 infants who received a first DTaP-IPV/Hib dose, 60.7% received HepB Dose 2 on the same day. Among 162,217 infants who received a third DTaP-IPV/Hib dose, 45.1% received HepB Dose 3 on the same day.Infants in the Northeast were less likely (OR=0.38, 95%CI=0.36-0.39), while those in the West were more likely (OR=1.41, 95%CI=1.36-1.46) than infants in the South to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day. Infants vaccinated by pediatricians (OR=0.54, 95%CI=0.53-0.55) were less likely to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day compared to infants vaccinated by family physicians. Infants who received PCV on the same day as the first dose of DTaP-IPV/Hib were more likely to receive HepB Dose 2 (OR=6.96, 95%CI=6.30-7.70) that day. These factors were also associated with co-administration of the third dose of DTaP-IPV/Hib and HepB Dose 3.ConclusionDifferences in co-administration of DTaP-IPV/Hib and HepB were associated with region of residence, provider type and co-administration of PCV. The reasons underlying these differences merit exploration. A hexavalent vaccine containing DTaP, IPV, Hib, and HepB could improve timeliness of HepB vaccination, while reducing the number of injections during infancy.DisclosuresTanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Zhiwen Liu, PhD, Merck & Co., Inc., (Employee) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

Hepatitis B Vaccination of Low Birth Weight Infants in Washington State.

The U.S. Advisory Committee on Immunization Practices (ACIP) recommends that infants born weighing less than 2,000 g receive the hepatitis B (HepB) vaccine at hospital discharge or 30 days of age. This study aimed to assess timely HepB vaccination among low birth weight infants. We hypothesized that many of these vulnerable infants would fail to receive their HepB birth dose on time. This retrospective cohort study included Washington State infants born weighing less than 2,000 g at an academic medical center between 2008 and 2013. Data were abstracted from electronic health records and linked to vaccine data from the Washington State Immunization Information System. Multivariable logistic regression was used to examine the associations between sociodemographic, clinical, and visit characteristics and HepB vaccination by birth hospitalization discharge or 30 days of age. Among 976 study infants, 58.4% received their HepB vaccine by birth hospitalization discharge or 30 days of age. Infants had higher odds of timely HepB vaccination if they were Hispanic (adjusted odds ratio [AOR] = 1.80, 95% confidence interval [CI]: 1.10-2.95) or non-Hispanic black (AOR = 2.28, 95% CI: 1.36-3.80) versus non-Hispanic white or if they were hospitalized 14 days or longer versus less than 14 days (AOR = 2.43, 95% CI: 1.66-3.54). Infants had lower odds of timely HepB vaccination if they were born before 34 weeks versus on or after 34 weeks of gestational age (AOR = 0.41, 95% CI: 0.27-0.63) or if they had an estimated household income less than $50,845 versus 50,845 or greater (AOR = 0.64, 95% CI: 0.48-0.86). Many infants born weighing less than 2,000 g did not receive their first HepB birth dose according to ACIP recommendations. Strategies are needed to improve timely HepB vaccination in this high-risk population. · Low birth weight infants are at increased risk for vaccine preventable diseases.. · Many of these vulnerable infants failed to receive their first hepatitis B vaccine on time.. · This study identified key factors associated with timely hepatitis B vaccination..

Epidemiological distribution of hepatitis B virus genotypes in 1–29-year-olds in the mainland of China

BackgroundTo analyze the epidemiological distribution of Hepatitis B virus (HBV) genotype in the mainland of China following the implementation of effective preventive measures. MethodsFive hundred and seventeen HBsAg-positive subjects aged 1–29 years surveyed in the 2014 national HBV sero-survey in the mainland of China were enrolled in the study. The full-length HBV genome was obtained by PCR amplification and sequencing. The HBV genotype was determined by phylogenetic analysis. Combined with questionnaire information, HBV genotype distribution was analyzed. ResultsOf the 517 HBsAg-positive subjects, 369 (71.4%) were included in the analysis. HBV genotypes found were B (45.0%), C (36.6%), D (6.0%), C/D (9.8%), B/C (2.2%), and I (0.5%). Geographic differences in HBV genotype were significant for seven regions. Three serotypes were found: adw (47.2%), adr (35.5%), and ayw (17.3%). B2 (43.9%) and C2 (25.2%) were the two major subgenotypes. The predominant genotypes differed between the Han group and the other ethnic groups. No statistical differences in genotype distribution were found by gender, age group, or hepatitis B (HepB) vaccination history. ConclusionThe prevalence of HBV genotype B was higher than that of genotype C with subgenotypes B2 and C2 endemic in 1–29-year-olds in the mainland of China, after HBV prevalence has reduced significantly due to the implementation of preventive measures. HepB vaccination or other factors did not interfere with HBV genotype distribution. The surveillance of HBV genotype was essential for responding to the potential changes and impact on the preventive policies in the future.

Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation

BackgroundThis study compares the immunogenicity and safety of a 3-antigen (S/pre-S1/pre-S2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia. MethodsWe conducted a randomized, double-blind, comparative study of 3-dose regimens of 3AV (10 μg) and 1AV (20 µg) in adults aged 18–45 years. We evaluated immunogenicity based on hepatitis B surface (HBs) antibody titers at days 1, 28, 90, 180, and 210, adverse and serious adverse events (SAEs) to study day 210. The primary outcome was based on the difference in rates of seroconversion at day 210 (lower bound 95% confidence interval [CI]: > − 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs ≥10 mIU/mL and anti-HBs geometric mean concentration (GMC). ResultsRate of seroconversion in 3AV (100%) was noninferior to 1AV (97.9%) at study day 210 (difference: 2.1%, 95% CI: −2.0, 6.3%]) but significantly higher at study day 28. SPR at study day 210 was >97% in both arms. Anti-HBs titers were significantly higher at study days 90 (P = .001) and 180 (P = .0001) with 3AV. Sex, age, and body mass index (BMI) had no impact on anti-HBs titers. The rates of local reactions related to vaccination were similar between vaccine arms (3AV vs 1AV) after the first (30% vs 18.8%, P = .15), second (20.0% vs 14.6%, P = .33), and third vaccination (14.9% vs 23.4%, P = .22). No SAEs were reported. Conclusions3AV was noninferior to 1AV. 3AV induced high SPR, and there were no safety concerns. Clinical Trials Registration. NCT04209400.

Protective effect of vaccinating infants with a 5\xa0\xb5g recombinant yeast-derived hepatitis B vaccine and the need for a booster dose in China

In 2002, China integrated hepatitis B vaccine (HepB) into its Expanded Program on Immunization (EPI) using HepB vaccine containing 5 µg of antigen. Although not recommended nationally, there was a common clinical practice in China of screening children for anti-HBs antibody level and giving a booster dose to HBV surface antigen (HBsAg)-negative children with non-protective anti-HBs antibody levels. We report an evaluation of the protective effectiveness of the 5 µg HepB vaccine and the serological response to the booster dose. We used data from a 2014 hepatitis B serological survey to determine HBsAg positivity and anti-HBs antibody levels among children who received and did not receive a booster dose. We determined HepB coverage from the Children Immunization Information Management System (CIIMS). We obtained and analyzed reports of acute Hepatitis B (AHB) during 2008–2014 obtained from the National Notifiable Disease Reporting System (NNDRS). The HBsAg-positive rate among children who had not received a booster dose was 0.41%, and did not increase with age (i.e., time since infant immunization). The anti-HBs positivity rate among the 6% of children who received a booster dose (88.41%) was higher than among those who had not received a booster (60.85%); anti-HBs antibody levels declined with age regardless of booster dose status. There was no statistically significant difference in HBsAg positivity between children who received a booster dose and those who did not. The AHB incidence among children born between 2002 and 2007 did not increase with age. Use of routine 5 µg HepB vaccine was not associated with an increase in AHB or of HBsAg positivity by time since vaccination, providing supportive evidence that individuals vaccinated with the 5 µg HepB vaccine do not need a booster dose. Although a booster dose was associated with increases in anti-HBs antibody levels, our study provided no evidence to support the need for this clinical practice. We should continue to strengthen serological monitoring of children, especially for those born to HBsAg positive mothers.

AS169 - High HBsAb titers consistent across 3 lots of the trivalent HepB vaccine, Sci-B-Vac: Results from the second pivotal phase 3 double-blind, randomized controlled trial designed to assess the lot-to-lot consistency of Sci-B-Vac in adults (CONSTANT)

AS169 - High HBsAb titers consistent across 3 lots of the trivalent HepB vaccine, Sci-B-Vac: Results from the second pivotal phase 3 double-blind, randomized controlled trial designed to assess the lot-to-lot consistency of Sci-B-Vac in adults (CONSTANT)

Higher proportion of responders with hepatitis B antibody levels ≥ 100 miu/ml with the trivalent HepB vaccine, Sci-B-Vac, compared to Engerix-B: results from the phase 3 double-blind, randomized study comparing immunogenicity and safety (PROTECT)

Higher proportion of responders with hepatitis B antibody levels ≥ 100 miu/ml with the trivalent HepB vaccine, Sci-B-Vac, compared to Engerix-B: results from the phase 3 double-blind, randomized study comparing immunogenicity and safety (PROTECT)

Improving the Neonatal Hepatitis B Vaccination Rate Through an Interdisciplinary, Multi-pronged Approach

Background: Annually, there are approximately 1000 new, preventable cases of neonatal Hepatitis B (HepB) infections in United States. The new American Academy of Pediatrics guidelines from August 2017 now recommend that all neonates meeting criteria be given the HepB vaccine within the first 24 hours of life. Among babies that contract HepB, 90% will develop chronic disease, compared to 15-30% of adults, and 25% will die prematurely from complications. Studies have shown that up to 95% of neonatal …

Lower Coverage Rates of Full Rotavirus Vaccine Series in Libyan Children: A Prospective Cross-Sectional Study, 2016

Background: There are little data on the current condition of national immunization programme (NIP) in Libya. In 2013, pentavalent rotavirus vaccines were added to the NIP. Incomplete rotavirus vaccine series may result in lower vaccine effectiveness. The study aimed to assess timeliness and coverage rates of routine NIP vaccinations including the newly introduced rotavirus vaccine in Libya. Methods: A prospective cross-sectional study of children aged 0 to 18 months was carried out in vaccination centers of two north-western cities. Data were collected during Nov-Dec 2016 from vaccination cards of children. Child age and doses received in previous visits were documented. Results: Overall, we included 1023 children assessed in 29 visits at six vaccination centers. In children aged 18 months, coverage rates for all doses of BCG, OPV, HepB, pneumococcal, Meningococcal and MMR vaccines exceeded 95%. Coverage rates for second and third doses of rotavirus vaccines were 89% and 68%, respectively. Most (75%) children who missed the third dose of rotavirus vaccine were aged &gt;8 months when at the time of appointment for the third dose. Conclusion: Overall, the coverage rate for routine vaccination in children assessed at immunization centers in northwest Libya was high. Lower coverage of full pentavalent rotavirus vaccine series may have been the result of exceeding the age restriction. Measures to improve timeliness of vaccination appointments should be assessed. Lifting the age restriction on rotavirus vaccines should be considered for at-risk population.

Game-Theoretical Model of Retroactive Hepatitis B Vaccination in China.

Hepatitis B (HepB) is one of the most common infectious diseases affecting over two billion people worldwide. About one third of all HepB cases are in China. In recent years, China made significant efforts to implement a nationwide HepB vaccination program and reduced the number of unvaccinated infants from 30 to 10%. However, many individuals still remain unprotected, particularly those born before 2003. Consequently, a catch-up retroactive vaccination is an important and potentially cost-effective way to reduce HepB prevalence. In this paper, we analyze a game theoretical model of HepB dynamics that incorporates government-provided vaccination at birth coupled with voluntary retroactive vaccinations. Given the uncertainty about the long-term efficacy of the HepB vaccinations, we study several scenarios. When the waning rate is relatively high, we show that this retroactive vaccination should be a necessary component of any HepB eradication effort. When the vaccine offers long-lasting protection, the voluntary retroactive vaccination brings the disease incidence to sufficiently low levels. Also, we find that the optimal vaccination rates are almost independent of the vaccination coverage at birth. Moreover, it is in an individual's self-interest to vaccinate (and potentially re-vaccinate) at a rate just slightly above the vaccine waning rate.

Improving Birth Dose Hepatitis B Vaccination Rates: A Quality Improvement Intervention.

There are 43 000 new cases of hepatitis B virus infection and 1000 cases of perinatally acquired infection each year in the United States. National recommendations are to administer hepatitis B (HepB) vaccine to all stable newborns >2000 g within 24 hours of birth. Our primary objective was to increase institutional vaccination rates from a baseline of 52% to goal >85% before hospital discharge. In February 2017, we instituted a multidisciplinary quality improvement project aimed at increasing HepB vaccination birth dose rates. Interventions included (1) standardizing the process of offering HepB vaccine via scripting and timing, (2) engaging and educating parents, and (3) educating physicians and nurses regarding the importance of HepB vaccination and strategies to discuss HepB vaccination with vaccine-hesitant parents. The main outcome measure was the percentage of newborns receiving HepB vaccination by discharge. The secondary outcome was the percentage of newborns receiving HepB vaccination by 12 hours of life per New York State Department of Health recommendation. Data were analyzed by using statistical process control P-charts. A total of 21 108 newborns were included between July 2015 and April 2019. In addition to several upward centerline shifts, implementation of interventions resulted in increased and sustained HepB vaccination rates by hospital discharge from a baseline of 52.4% to 72.5%. Rates by 12 hours of life increased from 21.5% to 42.5%. Multidisciplinary collaboration, scripting, and provider and staff education regarding the risks of hepatitis B virus, benefits of HepB vaccine, and strategies to discuss HepB vaccination with parents significantly increased vaccination rates. Further efforts to improve vaccination rates to within 12 hours are preferable.

Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea.

Background: Infection contributes to significant morbidity and mortality particularly in the very young and in low- and middle-income countries. While vaccines are a highly cost-effective tool against infectious disease little is known regarding the cellular and molecular pathways by which vaccines induce protection at an early age. Immunity is distinct in early life and greater precision is required in our understanding of mechanisms of early life protection to inform development of new pediatric vaccines.Methods and Analysis: We will apply transcriptomic, proteomic, metabolomic, multiplex cytokine/chemokine, adenosine deaminase, and flow cytometry immune cell phenotyping to delineate early cellular and molecular signatures that correspond to vaccine immunogenicity. This approach will be applied to a neonatal cohort in The Gambia (N ~ 720) receiving at birth: (1) Hepatitis B (HepB) vaccine alone, (2) Bacille Calmette Guerin (BCG) vaccine alone, or (3) HepB and BCG vaccines, (4) HepB and BCG vaccines delayed till day 10 at the latest. Each study participant will have a baseline peripheral blood sample drawn at DOL0 and a second blood sample at DOL1,−3, or−7 as well as late timepoints to assess HepB vaccine immunogenicity. Blood will be fractionated via a “small sample big data” standard operating procedure that enables multiple downstream systems biology assays. We will apply both univariate and multivariate frameworks and multi-OMIC data integration to identify features associated with anti-Hepatitis B (anti-HB) titer, an established correlate of protection. Cord blood sample collection from a subset of participants will enable human in vitro modeling to test mechanistic hypotheses identified in silico regarding vaccine action. Maternal anti-HB titer and the infant microbiome will also be correlated with our findings which will be validated in a smaller cohort in Papua New Guinea (N ~ 80).Ethics and Dissemination: The study has been approved by The Gambia Government/MRCG Joint Ethics Committee and The Boston Children's Hospital Institutional Review Board. Ethics review is ongoing with the Papua New Guinea Medical Research Advisory Committee. All de-identified data will be uploaded to public repositories following submission of study output for publication. Feedback meetings will be organized to disseminate output to the study communities.Clinical Trial Registration: Clinicaltrials.gov Registration Number: NCT03246230

Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus influenzae Type b Conjugate, and Hepatitis B Vaccine, and Guidance for Use in Infants.

On December 21, 2018 the Food and Drug Administration (FDA) licensed a hexavalent combined diphtheria and tetanus toxoids and acellular pertussis (DTaP) adsorbed, inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) conjugate (meningococcal protein conjugate) and hepatitis B (HepB) (recombinant) vaccine, DTaP-IPV-Hib-HepB (Vaxelis; MCM Vaccine Company),* for use as a 3-dose series in infants at ages 2, 4, and 6 months (1). On June 26, 2019, after reviewing data on safety and immunogenicity, the Advisory Committee on Immunization Practices (ACIP)† voted to include DTaP-IPV-Hib-HepB in the federal Vaccines for Children (VFC) program.§ This report summarizes the indications for DTaP-IPV-Hib-HepB and provides guidance for its use.

Long-term immunogenicity and immune memory response to the hepatitis B antigen in the RTS,S/AS01E malaria vaccine in African children: a randomized trial

ABSTRACT RTS,S/AS01E malaria vaccine contains the hepatitis B virus surface antigen and may thus serve as a potential hepatitis B vaccine. To evaluate the impact of RTS,S/AS01E when implemented in the Expanded Program of Immunization, infants 8–12 weeks old were randomized to receive either RTS,S/AS01E or a licensed hepatitis B control vaccine (HepB), both co-administered with various combinations of the following childhood vaccines: diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b, trivalent oral poliovirus, pneumococcal non-typeable Haemophilus influenzae protein D conjugate and human rotavirus vaccine. Long-term persistence of antibodies against the circumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) were assessed, together with the immune memory response to the HB antigen following a booster dose of HepB vaccine. Subgroups receiving RTS,S or the HepB control vaccine were pooled into RTS,S groups and HepB groups, respectively. One month post-HepB booster vaccination, 100% of participants in the RTS,S groups and 98.3% in the control groups had anti-HBs antibody concentrations ≥10 mIU/mL with the geometric mean concentrations (GMCs) at 46634.7 mIU/mL (95% CI: 40561.3; 53617.6) and 9258.2 mIU/mL (95% CI: 6925.3; 12377.0), respectively. Forty-eight months post-primary vaccination anti-CS antibody GMCs ranged from 2.3 EU/mL to 2.7 EU/mL in the RTS,S groups compared to 1.1 EU/mL in the control groups. Hepatitis B priming with the RTS,S/AS01E vaccine was effective and resulted in a memory response to HBsAg as shown by the robust booster response following an additional dose of HepB vaccine. RTS,S/AS01E when co-administered with PHiD-CV, HRV and other childhood vaccines, had an acceptable safety profile.

Seroprevalence of Anti-HBs Titers in Health-care Workers in a Tertiary Care Hospital in Mumbai

Introduction: Hepatitis B is a vaccine preventable disease caused by Hepatitis B virus which is a partially double stranded virus. Sharp injuries are the most common occupational injuries among healthcare workers (HCW). HCW are prone to sharp injuries during work, and infection after exposure. Materials and Methods: Anti-HBs titres were measured in 231 HCW in a tertiary care hospital in Mumbai. Result: Eighty six males and 145 females participated in the study. Out of these 41 were vaccine non compliant; 37 were partially immunized and 4 were not immunized. 32 out of 231 individuals tested had titres below 10 mIU/ml (10 mIU/ml considered to be the minimal protective titre). Among the individuals who had titres <10 mIU/ml, 17 were medical assistants, 10 were nursing officers and 5 were doctors. Out of these there were 04 who had not received any HepB vaccination in the past. The rest had received either complete or partial immunization. All those who had completed primary vaccination series and had titres <10 mIU/ml (n = 14) had completed primary vaccination more than 5 years ago. Conclusions: In our study 82.2% were vaccine compliant and 27.8% were vaccine non compliant. Out of 231 individuals 32 (13.85%) had titres <10 mIU/ml. This study highlights the need for HCW to undergo anti-HBs titres post primary vaccination and after 5 years of primary vaccination to identify susceptible individuals. The HCW with non protective titres should be give Hep B booster and antibody levels should be tested to confirm protective titres.

LB13. Trivalent Hepatitis B (HepB) Vaccine Yields Superior Seroprotection Rates in Adults: Results from the Phase 3 Double-Blind, Randomized Study Comparing Immunogenicity and Safety of a 3-Dose Regimen of Sci-B-Vac™ and Engerix B® (PROTECT)

BackgroundMany adults fail to achieve seroprotection after receiving 3 doses of monovalent HepB vaccines such as Engerix-B® and the response decreases with age and with common co-morbidities. Sci-B-Vac™ is a trivalent HepB vaccine produced in mammalian cells, adjuvanted with aluminum hydroxide, which in addition to small S antigen, contains preS1 and preS2 antigens expressing highly immunogenic T- and B-cell epitopes that may enhance seroprotection rates (SPR) in adults.MethodsIn a multicentre study, the immunogenicity of 10 µg dose of Sci-B-Vac™ was compared with a 20-µg dose of Engerix-B® given at days 0, 28, and 168 (NCT03393754). Randomization was stratified by study center and age (18–44, 45–64, ≥65 years). Immunogenicity, including SPR (% subjects with anti-HBs levels ≥10 mIU/mL), and safety outcomes were followed to Day 336. The co-primary objectives were (1) non-inferiority in adults ≥18 years and (2) superiority in adults ≥45 years of SPR, 4 weeks after the third dose.ResultsOf 1,607 randomized subjects, 42.3% were from United States, 41.6% EU, and 16.1% Canada. Males (38.5%) and females (61.5%) were enrolled to 18–44 (18.6%), 45–64 (44.6%), and ≥ 65 year (36.8%) age groups. Both co-primary endpoints were met. In the non-inferiority analysis, SPR in Sci-B-Vac™ recipients aged ≥18 years was 91.4% vs. 76.5% for Engerix-B®; SPR difference: 14.9%; 95% confidence interval (CI) [11.2%, 18.6%]. Superiority analysis showed that SPR in Sci-B-Vac™ recipients aged ≥45 years was 89.4% vs. 73.1% for Engerix-B®—SPR difference: 16.4%; 95% CI [12.2%, 20.7%] (figure). Significantly higher SPR for Sci-B-Vac™ vs. Engerix-B® was noted in subgroups (gender, BMI, diabetes, smoking and particularly age—SPR difference for 45–64 (14.7% [9.8–19.8%]) and ≥ 65 (18.9% [11.6–26.1%]) years. No major safety signals were observed; solicited and unsolicited adverse events were consistent with the known vaccine safety profiles.ConclusionSci-B-Vac™ met immunogenicity endpoints for non-inferiority in adults aged ≥ 8 years and was superior in adults aged ≥45 years, compared with the monovalent vaccine, Engerix-B®. Sci-B-Vac™ SPR was higher compared with Engerix-B® in key subgroups. No safety signals were observed and safety and tolerability were consistent with the known profile of Sci-B-Vac™. DisclosuresTimo Vesikari, MD, VBI (Grant/Research Support, I have received funding from VBI to carry out the reported clinical trial in Finland), Joanne M. Langley, MD, VBI Vaccines (Grant/Research Support), Johanna Spaans, BSc, MSc, VBI Vaccines (Employee), Nathalie Machluf, PhD, SciVac Ltd. (Employee), Dave Anderson, PhD, VBI Vaccines, Inc. (Employee, Shareholder), Vlad Popovic, MD, VBI Vaccines (Employee), Francisco Diaz-Mitoma, MD, VBI Vaccines, Inc. (Consultant, Shareholder, Independent Contractor). Other Authors: No reported disclosures.

Challenges with hepatitis B vaccination of high risk adults – A pilot program

BackgroundAcute hepatitis B virus (HBV) infections in the United States occur predominantly among persons aged 30–59 years. The Centers for Disease Control and Prevention (CDC) recommends vaccination of adults at increased risk for HBV infection. Completing the hepatitis B (HepB) vaccine dose-series is critical for optimal immune response. ObjectivesCDC funded 14 health departments (awardees) from 2012 to 2015 to implement a pilot HepB vaccination program for high-risk adults. We evaluated the pilot program to assess vaccine utilization; vaccine dose-series completion, including by vaccination location type; and implementation challenges. MethodsAwardees collaborated with sites providing health care to persons at increased risk for HBV infection. Awardees collected information on doses administered, vaccine dose-series completion, and challenges completing and tracking vaccinations, including use of immunization information systems (IIS). Data were reported by each awardee in aggregate to CDC. ResultsSix of 14 awardees administered 47,911 doses and were able to report patient-level dose-series completion. Among persons who received dose 1, 40.4% received dose 2, and 22.3% received dose 3. Local health department clinics had the highest 3–dose-series completion, 60.6% (531/876), followed by federally qualified health centers at 38.0% (923/2432). While sexually transmitted diseases (STD) clinics administered the most doses in total (17,173 [35.8% of 47,911 doses]), 3–dose-series completion was low (17.1%). The 14 awardees reported challenges regarding completing and tracking dose-series, including reaching high-risk adults for follow-up and inconsistencies in use of IIS or other tracking systems across sites. ConclusionsDose-series completion was low in all settings, but lowest where patients may be less likely to return for follow-up (e.g., STD clinics). Routinely assessing HepB vaccination needs of high-risk adults, including through use of IIS where available, may facilitate HepB vaccine dose-series completion.