Hepatitis B-CpG Vaccine Series for Healthcare Workers Who Are Hepatitis B Vaccine Nonresponders.

This prospective study enrolled healthcare workers (HCWs) who were nonresponders following at least 5 doses of aluminum-adjuvanted hepatitis B vaccine who received the 2-dose Heplisav-B (HepB-CpG) (Dynavax Technologies Corporation, Emeryville, CA) series. After 2 doses of HepB-CpG, 43/47 (91%) participants, and with 1 dose, 41/49 (84%) responded. HepB-CpG could be the preferred vaccine in HCW nonresponders. Clinical Trials Registration. Clinicaltrials.gov NCT04456504.

Assessing vaccine-induced immunity against pneumococcus, hepatitis A and B over a 9-year follow-up in pediatric liver transplant recipients: A nationwide retrospective study.

Pediatric liver transplant recipients are particularly at risk of infections. The most cost-effective way to prevent infectious complications is through vaccination, which can potentially prevent infections due to hepatitis B (HBV) virus, hepatitis A virus (HAV), and invasive pneumococcal diseases. Here, we performed a retrospective analysis of HBV, HAV, and pneumococcal immunity in pediatric liver transplant recipients between January 1, 2009, and December 31, 2020, to collect data on immunization and vaccine serology. A total of 94% (58/62) patients had available vaccination records. At transplant, 90% (45/50) were seroprotected against HBV, 63% (19/30) against HAV, and 78% (18/23) had pneumococcal immunity, but immunity against these 3 pathogens remained suboptimal during the 9-year follow-up. A booster vaccine was administered to only 20% to 40% of patients. Children who had received >4 doses of HBV vaccine and > 2 doses of HAV vaccine pretransplant displayed a higher overall seroprotection over time post-solid organ transplant. Our findings suggest that a serology-based approach should be accompanied by a more systematic follow-up of vaccination, with special attention paid to patients with an incomplete vaccination status at time of transplant.

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.

Progress Toward the Elimination of Hepatitis B and Hepatitis C in the Country of Georgia, April 2015-April 2024.

Hepatitis B and hepatitis C are leading causes of cirrhosis and liver cancer and caused 1.3 million deaths worldwide in 2022. Hepatitis B is preventable with vaccination, and hepatitis C is curable with direct-acting antivirals. In 2015, in collaboration with CDC and other partners, Georgia, a country at the intersection of Europe and Asia, launched a hepatitis C elimination program to reduce the prevalence of chronic hepatitis C; at that time, the prevalence was 5.4%, more than five times the global average of 1.0%. In 2016, the World Health Assembly endorsed a goal for the elimination of viral hepatitis as a public health problem by 2030. In 2024, 89% of the Georgian adult population have received screening for hepatitis C, 83% of persons with current chronic HCV infection have received a diagnosis, and 86% of those with diagnosed hepatitis C have started treatment. During 2015-2023, vaccination coverage with the hepatitis B birth dose and with 3 doses of hepatitis B vaccine among infants exceeded 90% for most years. In 2021, the prevalence of hepatitis B surface antigen was 0.03% among children and adolescents aged 5-17 years and 2.7% among adults. Georgia has demonstrated substantial progress toward hepatitis B and hepatitis C elimination. Using lessons from the hepatitis C elimination program, scale-up of screening and treatment for hepatitis B among adults would prevent further viral hepatitis-associated morbidity and mortality in Georgia and would accelerate progress toward hepatitis B and hepatitis C elimination by 2030.

Progress Toward Elimination of Mother-to-Child Transmission of Hepatitis B Virus - Region of the Americas, 2012-2022.

In 2022, an estimated 5 million persons in the World Health Organization Region of the Americas (AMR) were living with chronic hepatitis B virus (HBV) infection, the leading cause of hepatocellular carcinoma and cirrhosis worldwide. Most chronic infections are acquired through mother-to-child transmission (MTCT) or horizontal transmission during childhood and are preventable with hepatitis B vaccination, including a birth dose (HepB-BD), followed by 2-3 additional doses (HepB3) in infancy. The Pan American Health Organization (PAHO) Elimination of MTCT of HBV infection strategy is intended to reduce chronic HBV infection (measured by hepatitis B surface antigen [HBsAg] seroprevalence) to ≤0.1% among children by achieving 1) ≥95% coverage with HepB-BD and HepB3; and 2) ≥80% of pregnant women received testing for HBsAg, and provision of hepatitis B immunoglobulin to HBV-exposed neonates. By 2012, all 51 AMR countries and territories (countries) provided HepB3 nationwide, and by 2021, 34 (67%) provided HepB-BD nationwide. Mathematical models estimate that HBsAg seroprevalence in children is ≤0.1% in 14 (28%) of 51 countries and at the regional level. Three (6%) of 51 countries met the 95% coverage targets for both HepB3 and HepB-BD during both 2021 and 2022. Of these, two have likely met criteria for the elimination of MTCT of HBV infection. However, in 2022, HepB3 coverage had declined by ≥10 percentage points in 15 (37%) of 41 countries with 2012 coverage data for comparison. These declines in HepB3 coverage, as well as the absence of HepB-BD in the routine immunization schedules in 17 countries, threaten PAHO's progress toward the elimination of MTCT of HBV infection. Efforts to introduce HepB-BD and maintain high HepB3 and HepB-BD coverage are needed.

Knowledge of hepatitis B infection, hepatitis B vaccine, and vaccination status with its associated factors among healthcare workers in Kampot and Kep Provinces, Cambodia.

BACKGROUND: Healthcare Workers (HCWs) are susceptible to hepatitis B virus (HBV) infection and are advised to receive vaccination. However, vaccination rates remain low in developing countries. There is little data concerning Hepatitis B (HepB) vaccination and information regarding HBV knowledge among HCWs in Cambodia. This study aimed to evaluate the knowledge of HBV infection, HepB vaccine, and vaccination status with its associated factors among HCWs in Cambodia. METHODS: A Cross-sectional study was conducted among HCWs in Kampot and Kep Provinces, Cambodia, from September to October 2023 using a questionnaire survey. A total of 261 HCWs were recruited from 1,309 individuals working in all 83 health facilities using systematic random sampling methods. Statistical analyses including the χ2-test and multivariate logistic regression were conducted to identify factors associated with vaccination among the participants. RESULTS: Among 259 participants, 62.9% showed good knowledge of HBV infection, and 65.6% demonstrated good knowledge of the HepB vaccine. 59.8% of the participants had received the HepB vaccine, while 40.2% remained unvaccinated. Analysis showed that HCWs working at Provincial Health Department/Operational Districts and Provincial Referral Hospital/Referral Hospitals were more likely to be vaccinated compared to those at Health Centers [AOR = 6.5; CI = 1.1-39.5, p = 0.0403; AOR = 2.8, CI = 1.0-7.8, p = 0.0412], respectively. Furthermore, individuals with good knowledge of the HBV infection and vaccine were more likely to receive the vaccine compared to those with inadequate knowledge [AOR = 6.3; CI = 3.3-12.3, p < .0001; AOR = 3.7, CI = 1.9-7.4, p = 0.0001], respectively. Within the unvaccinated HCWs, 32% reported high vaccine costs as a barrier, 33% mentioned workplace vaccine was not for adults, and 59% reported insufficient education on adult HepB vaccination. CONCLUSIONS: The HepB vaccination coverage among HCWs is at 59.8%, which is below the World Health Organization's (WHO) recommendation rate of 100%. Knowledge of HBV infection and HepB vaccine were good predictive factors for vaccination. The high cost of vaccine, workplace vaccine not for adults, and insufficient education on adult vaccination were found as barriers to vaccination. This study underscores the importance of providing education to HCWs on HBV infection and the HepB vaccine. Furthermore, it highlights the need for a policy that ensures free vaccination for HCWs.

Low HBV knowledge is associated with low HBV vaccination uptake in general adult population despite incentivization of HBV vaccination.

BACKGROUND: Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. METHODS: After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants' receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. RESULTS: 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1-14.3%), and 8.9% (95%CI 5.6-12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12-5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38-13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07-3.87). CONCLUSION: We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.

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.

Hepatitis B Birth Dose Vaccination Improvement Initiative: The 24-Hour Baby Bundle.

BACKGROUND: An estimated 25,000 infants are born to mothers diagnosed with hepatitis B virus (HBV) each year in the United States. Administration of the birth dose HBV vaccine prevents transmission during delivery. Despite national guidelines promoting vaccination within 24 hours of birth, fewer than 70% of infants receive the dose in their first 3 days of life. To improve compliance with national recommendations, Northwestern Medicine implemented a bundled care initiative in the well newborn nursery, entitled the 24-hour baby bundle (24-HBB). PURPOSE: Evaluate the 24-HBB's effect on improving time to HBV vaccine administration. METHODS: The 24-HBB was created by an interdisciplinary team and implemented on February 17, 2020. Bundled care begins at 23 hours of life, starting with the HBV vaccine, followed by bath, weight, and congenital heart disease screening, and ending with metabolic screening. We conducted a retrospective cohort study of 22,057 infants born at Northwestern Medicine Prentice Women's Hospital in Chicago, Illinois. Our sample included preintervention birthdates between February 16, 2019, and January 16, 2020, and postintervention birthdates between March 17, 2020, and February 16, 2021, with a 2-month washout education period between January 17, 2020, and March 16, 2020. RESULTS: Hepatitis B virus immunization within 24 hours increased significantly from 43.83% to 66.90% (P < .0001). In addition, overall hepatitis B immunization prior to discharge significantly increased after implementation of the 24-HBB (98.18% vs 98.82%, P < .0001). IMPLICATIONS FOR PRACTICE AND RESEARCH: The 24-HBB is effective at increasing rates of HBV immunization within 24 hours of birth. Newborn nurseries may benefit from similar initiatives to prevent hepatitis B infection, satisfy national recommendations, and promote childhood vaccination compliance.

High-Dose Vitamin D3 and Tonsillectomy as Therapeutic Management in Henoch-Schönlein Purpura Following Hepatitis B Vaccination: A Rare Case Report.

Henoch-Schönlein purpura (HSP) is an immunoglobulin A (IgA)-mediated systemic vasculitis, which is one of the rare adverse reactions to hepatitis B vaccination. Low vitamin D levels were found to be present in the majority of HSP patients.A 19-year-old woman was admitted with a purpuric rash on bilateral lower limbs and joint pain on her left index finger in January 2020. A previous history of rash occurred one week after the patient received her first dose of recombinant hepatitis-B vaccination. Routine hematological examination, creatinine, urinalysis, C3, and C4 showed normal results. HBsAg, Anti-HCV, and ANA tests were negative, and anti-HBs were elevated. Vitamin D is very low. The patient was diagnosed with HSP and given mycophenolate mofetil, methylprednisolone, vitamin D3, and folic acid. Within 1 month of therapy, the rash still occurred frequently, so mycophenolate mofetil was changed to mycophenolic acid, the dose of methylprednisolone was increased and fexofenadine was administered. In the next 3 months, the rash has improved. However, patients reported knee joint pain and hair loss. In May 2021, the patient underwent tonsillectomy due to acute exacerbation of chronic tonsillitis. Thereafter, the patient reported that the rash had completely resolved and never worsened, and the vitamin D assay was normal.Hepatitis B vaccination is one of the etiologies of HSP, although it is rare, so it is important to ask about the vaccination history in patients with suspected HSP. Correction of vitamin D and performing tonsillectomy provide better treatment results in HSP cases in this patient.

[Accelerating the elimination of hepatitis B virus infection: expert recommendations for expanding prevention and treatment].

In order to achieve the early goal of "eliminating viral hepatitis as a public health threat by 2030" as proposed by the World Health Organization, the relevant issues that have not yet reached consensus on the aspects of hepatitis B prevention and treatment, including population-wide screening, adult hepatitis B vaccination, the evaluation of quantitative values of hepatitis B virus DNA, the alanine aminotransferase threshold for initiating antiviral therapy, the treatment of patients in the "indeterminate phase," the treatment of patients with co-infections and comorbidities, and others. Thus, experts have formulated recommendations to further expand hepatitis B prevention and treatment, with the aim of accelerating the elimination of hepatitis B virus infection.

Toward reaching hepatitis B goals: hepatitis B epidemiology and the impact of two decades of vaccination, Georgia, 2021.

BackgroundGeorgia has adopted the World Health Organization European Region's and global goals to eliminate viral hepatitis. A nationwide serosurvey among adults in 2015 showed 2.9% prevalence for hepatitis B virus (HBV) surface antigen (HBsAg) and 25.9% for antibodies against HBV core antigen (anti-HBc). HBV infection prevalence among children had previously not been assessed.AimWe aimed to assess HBV infection prevalence among children and update estimates for adults in Georgia.MethodsThis nationwide cross-sectional serosurvey conducted in 2021 among persons aged ≥ 5 years used multi-stage stratified cluster design. Participants aged 5-20 years were eligible for hepatitis B vaccination as infants. Blood samples were tested for anti-HBc and, if positive, for HBsAg. Weighted proportions and 95% confidence intervals (CI) were calculated for both markers.ResultsAmong 5-17 year-olds (n = 1,473), 0.03% (95% CI: 0-0.19) were HBsAg-positive and 0.7% (95% CI: 0.3-1.6) were anti-HBc-positive. Among adults (n = 7,237), 2.7% (95% CI: 2.3-3.4) were HBsAg-positive and 21.7% (95% CI: 20.4-23.2) anti-HBc-positive; HBsAg prevalence was lowest (0.2%; 95% CI: 0.0-1.5) among 18-23-year-olds and highest (8.6%; 95% CI: 6.1-12.1) among 35-39-year-olds.ConclusionsHepatitis B vaccination in Georgia had remarkable impact. In 2021, HBsAg prevalence among children was well below the 0.5% hepatitis B control target of the European Region and met the ≤ 0.1% HBsAg seroprevalence target for elimination of mother-to-child transmission of HBV. Chronic HBV infection remains a problem among adults born before vaccine introduction. Screening, treatment and preventive interventions among adults, and sustained high immunisation coverage among children, can help eliminate hepatitis B in Georgia by 2030.

Dissolving Microneedle Arrays as a Hepatitis B Vaccine Delivery System Adjuvanted by APC-Targeted Poly (Lactic-co-Glycolic Acid) (PLGA) Nanoparticles.

The objective of this study is to develop a new hepatitis B surface antigen (HBsAg) delivery system by coating soluble microneedle arrays with mannose-modified PLGA nanoparticles (MNPs). MNPs of different sizes were synthesized. The effects these nanoparticles on the maturation of dendritic cells were studied by flow cytometry. HBsAg-containing MNPs (HBsAg/MNPs) of the appropriate sizes were coated into water-soluble microneedle arrays. The in vitro characteristics of microneedles arrays and the immune responses after subcutaneous administration in mice were studied. The results showed that PLGA nanoparticles with an average size of about 800 nm showed the most significant effects in stimulating the maturation of dendritic cells. In the water-soluble microneedle array, the targeted PLGA nanoparticles containing HBsAg were distributed discretely with a maximum distribution height of about 280 µm with a drug load of 0.98 ± 0.05 µg/mg. The drug-containing microneedle arrays exhibited excellent mechanical properties and improved biosafety. The results of immune responses in vivo showed that the subcutaneous administration of the microneedle arrays induced the proliferation of splenocyte, secreted specific IL-12 and IFN-γ, and promote the production of IgG in mice. This study verifies the feasibility of soluble composited microneedles administration in hepatitis B immunization, and provides new ideas for the development and application of non-injectable vaccine delivery systems.

Generation of HBsAg-reactive T- and B-cells following HBV vaccination in serological non-responders under hemodialysis treatment.

HBV vaccination is recommend for hemodialysis patients, but only 50-60% of the patients show seroconversion. HBV vaccine-induced generation of HBV reactive T and B cells could be detected regardless of their capacity to mount a serological response, indicating that patients without seroconversion are potentially protected by their HBV-reactive T cell pool.

Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction.

Importance: The 2-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) generated higher seroprotection in prelicensure trials than did a 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine; Engerix-B). However, in 1 trial, a higher number of acute myocardial infarction (MI) events were observed among those who received the HepB-CpG vaccine than among those who received the HepB-alum vaccine, an outcome requiring further study. Objective: To compare the rate of acute MI between recipients of HepB-CpG vaccine and HepB-alum vaccine. Design, Setting, and Participants: This prospective cohort noninferiority study was conducted at Kaiser Permanente Southern California (KPSC), an integrated health care system with 15 medical centers and approximately 4.7 million members. The study included 69 625 adults not undergoing dialysis who received at least 1 dose of a hepatitis B vaccine in either family medicine or internal medicine departments at KPSC from August 7, 2018, to October 31, 2019 (November 30, 2020, final follow-up). Exposures: Receipt of HepB-CpG vaccine vs HepB-alum vaccine. The first dose during the study period was the index dose. Main Outcomes and Measures: Individuals were followed up for 13 months after the index dose for occurrence of type 1 acute MI. Potential events were identified using diagnosis codes and adjudicated by cardiologists. The adjusted hazard ratio (HR) of acute MI was estimated comparing recipients of HepB-CpG vaccine with recipients of HepB-alum vaccine, with inverse probability of treatment weighting (IPTW) to adjust for demographic and clinical characteristics. The upper limit of the 1-sided 97.5% CI was compared with a noninferiority margin of 2. Results: Of the 31 183 recipients of HepB-CpG vaccine (median age, 49 years; IQR, 38-56 years), 51.2% (n = 15 965) were men, and 52.7% (n = 16 423) were Hispanic. Of the 38 442 recipients of HepB-alum (median age, 49 years; IQR, 39-56 years), 50.8% (19 533) were men, and 47.1% (n = 18 125) were Hispanic. Characteristics were well-balanced between vaccine groups after IPTW. Fifty-two type 1 acute MI events were confirmed among recipients of HepB-CpG vaccine for a rate of 1.67 per 1000-person-years, and 71 type 1 acute MI events were confirmed among recipients of HepB-alum vaccine for a rate of 1.86 per 1000 person-years (absolute rate difference, -0.19 [95% CI, -0.82 to 0.44]; adjusted HR, 0.92 [1-sided 97.5% CI, ∞ to 1.32], which was below the noninferiority margin; P < .001 for noninferiority). Conclusions and Relevance: In this cohort study, receipt of HepB-CpG vaccine compared with HepB-alum vaccine did not meet the statistical criterion for increased risk of acute myocardial infarction.

Knockdown of Virus Antigen Expression Increases Therapeutic Vaccine Efficacy in High-Titer Hepatitis B Virus Carrier Mice.

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection persists because the virus-specific immune response is dysfunctional. Therapeutic vaccines might be used to end immune tolerance to the virus in patients with chronic infection, but these have not been effective in patients so far. In patients with chronic HBV infection, high levels of virus antigens might prevent induction of HBV-specific immune responses. We investigated whether knocking down expression levels of HBV antigens in liver might increase the efficacy of HBV vaccines in mice. METHODS: We performed studies with male C57BL/6 mice that persistently replicate HBV (genotype D, serotype ayw)-either from a transgene or after infection with an adeno-associated virus that transferred an overlength HBV genome-and expressed HB surface antigen at levels relevant to patients. Small hairpin or small interfering (si)RNAs against the common 3'-end of all HBV transcripts were used to knock down antigen expression in mouse hepatocytes. siRNAs were chemically stabilized and conjugated to N-acetylgalactosamine to increase liver uptake. Control mice were given either entecavir or non-HBV-specific siRNAs and vaccine components. Eight to 12 weeks later, mice were immunized twice with a mixture of adjuvanted HBV S and core antigen, followed by a modified Vaccinia virus Ankara vector to induce HBV-specific B- and T-cell responses. Serum and liver samples were collected and analyzed for HBV-specific immune responses, liver damage, and viral parameters. RESULTS: In both models of HBV infection, mice that express hepatocyte-specific small hairpin RNAs or that were given subcutaneous injections of siRNAs had reduced levels of HBV antigens, HBV replication, and viremia (1-3 log10 reduction) compared to mice given control RNAs. Vaccination induced production of HBV-neutralizing antibodies and increased numbers and functionality of HBV-specific, CD8+ T cells in mice with low, but not in mice with high, levels of HBV antigen. Mice with initially high titers of HBV and knockdown of HBV antigen expression, but not mice with reduced viremia after administration of entecavir, developed polyfunctional, HBV-specific CD8+ T cells, and HBV was eliminated. CONCLUSIONS: In mice with high levels of HBV replication, knockdown of HBV antigen expression along with a therapeutic vaccination strategy, but not knockdown alone, increased numbers of effector T cells and eliminated the virus. These findings indicate that high titers of virus antigens reduce the efficacy of therapeutic vaccination. Anti-HBV siRNAs and therapeutic vaccines are each being tested in clinical trials-their combination might cure chronic HBV infection.

Progress Toward Hepatitis B Control - World Health Organization European Region, 2016-2019.

In 2019, an estimated 14 million persons in the World Health Organization (WHO) European Region* (EUR) were chronically infected with hepatitis B virus (HBV), and approximately 43,000 of these persons died from complications of chronic HBV infection (1). In 2016, the WHO Regional Office for Europe set hepatitis B control program targets for 2020, including 1) ≥90% coverage with 3 doses of hepatitis B vaccine (HepB3), 2) ≥90% coverage with interventions to prevent mother-to-child transmission (MTCT) of HBV,† and 3) ≤0.5% prevalence of HBV surface antigen (HBsAg)§ in age groups eligible for vaccination with hepatitis B vaccine (HepB) (2-4). This report describes the progress made toward hepatitis B control in EUR during 2016-2019. By December 2019, 50 (94%) of 53 countries in EUR provided routine vaccination with HepB to all infants or children aged 1-12 years (universal HepB), including 23 (43%) countries that offered hepatitis B birth dose (HepB-BD) to all newborns. In addition, 35 (73%) of the 48 countries with universal infant HepB vaccination reached ≥90% HepB3 coverage annually during 2017-2019, and 19 (83%) of the 23 countries with universal birth dose administration achieved ≥90% timely HepB-BD coverage¶ annually during that period. Antenatal hepatitis B screening coverage was ≥90% in 17 (57%) of 30 countries that selectively provided HepB-BD to infants born to mothers with positive HBsAg test results. In January 2020, Italy and the Netherlands became the first counties in EUR to be validated to have achieved the regional hepatitis B control targets. Countries can accelerate progress toward hepatitis B control by improving coverage with HepB and interventions to prevent MTCT and documenting achievement of the HBsAg seroprevalence target through representative serosurveys or, in low-endemicity countries, antenatal screening.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study.

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Two-Dose Hepatitis B Vaccine (Heplisav-B) Results in Better Seroconversion Than Three-Dose Vaccine (Engerix-B) in Chronic Liver Disease.

BACKGROUND: The efficacy of the two-dose hepatitis B virus (HBV) vaccine (Heplisav-B®) in patients with chronic liver disease (CLD) is unknown. AIMS: To compare the immunogenicity achieved with Heplisav-B and the conventional three-dose vaccine (Engerix-B®) in patients with CLD, and to identify factors that predict seroconversion. METHODS: We retrospectively identified all adults who completed Heplisav-B or Engerix-B regimens from August 1, 2015, to January 31, 2019. Post-vaccination immunity was assessed by quantitative HBV surface antibody (HBsAb) measurement. RESULTS: We identified 166 patients (106 Engerix-B and 60 Heplisav-B) with chronic liver disease (mean age 59.0 ± 11.3 years, 52% male, 34% cirrhosis, mean MELD score of those with cirrhosis 10.1 ± 5.4) who had completed the vaccinations and had data available on post-vaccination HBsAb levels at least 2 months after completion of the vaccine regimen. Seroprotective HBsAb levels (> 10 mIU/ml) were achieved in 63% with Heplisav-B and in 45% with Engerix-B (p = 0.03). Univariable analysis showed that age (p = 0.01), insurance (p = 0.02), renal failure (p = 0.02), COPD (p = 0.05), and cirrhosis (p < 0.01) had a significant effect on achieving immunogenicity. On multivariable analysis, patients with cirrhosis (adjusted odds ratio [aOR]: 0.27, 95% CI 0.13-0.55), COPD (aOR: 0.06, 95% CI 0.01-0.56), or renal failure (aOR 0.36, 95% CI 0.14-0.93) had a lower likelihood of achieving immunity, and patients who received Heplisav-B® had a 2.7-fold greater likelihood of achieving immunity than those who received Engerix-B® (aOR: 2.74, 95% CI 1.31-5.71). CONCLUSION: The two-dose recombinant hepatitis B vaccine resulted in better seroconversion than the three-dose vaccine. Cirrhosis, COPD, and renal failure were associated with a lower likelihood of achieving immunogenicity.

Chimeric Virus-Like Particles of Prawn Nodavirus Displaying Hepatitis B Virus Immunodominant Region: Biophysical Properties and Cytokine Response.

Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines available in the market. Thus, it is important to develop a more protective vaccine. Previously, we showed that hepatitis B virus (HBV) 'a' determinant (aD) displayed on the prawn nodavirus capsid (Nc) and expressed in Spodoptera frugiperda (Sf9) cells (namely, Nc-aD-Sf9) self-assembled into virus-like particles (VLPs). Immunisation of BALB/c mice with the Nc-aD-Sf9 VLPs showed significant induction of humoral, cellular and memory B-cell immunity. In the present study, the biophysical properties of the Nc-aD-Sf9 VLPs were studied using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the antigenicity of the Nc-aD-Sf9 VLPs, and multiplex ELISA was employed to quantify the cytokine response induced by the VLPs administered intramuscularly into BALB/c mice (n = 8). CD spectroscopy of Nc-aD-Sf9 VLPs showed that the secondary structure of the VLPs predominantly consisted of beta (ß)-sheets (44.8%), and they were thermally stable up to ~52 °C. ELISA revealed that the aD epitope of the VLPs was significantly antigenic to anti-HBV surface antigen (HBsAg) antibodies. In addition, multiplex ELISA of serum samples from the vaccinated mice showed a significant induction (p < 0.001) of IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-12p70. This cytokine profile is indicative of natural killer cell, macrophage, dendritic cell and cytotoxic T-lymphocyte activities, which suggests a prophylactic innate and adaptive cellular immune response mediated by Nc-aD-Sf9 VLPs. Interestingly, Nc-aD-Sf9 induced a more robust release of the aforementioned cytokines than that of Nc-aD VLPs produced in Escherichia coli and a commercially used hepatitis B vaccine. Overall, Nc-aD-Sf9 VLPs are thermally stable and significantly antigenic, demonstrating their potential as an HBV vaccine candidate.