Immunogenicity and Safety of Hepatitis B Virus (HBV) Vaccine With a Toll-Like Receptor 9 Agonist Adjuvant in HBV Vaccine-Naïve People With Human Immunodeficiency Virus.

In this international, multicenter open-label study (ACTG A5379) of HepB-CpG vaccine in people with human immunodeficiency virus (HIV) without prior hepatitis B virus (HBV) vaccination, all 68 participants achieved HBV seroprotective titers after the 3-dose series in the primary analysis. No unexpected safety issues were observed.

A real world comparison of HepB (Engerix-B®) and HepB-CpG (Heplisav-B®) vaccine seroprotection in patients receiving maintenance dialysis.

BACKGROUND: Vaccination against hepatitis B virus (HBV) is recommended for dialysis patients. Two reports comparing seroprotection (SP) rates following HepB and HepB-CpG in vaccine-naïve patients with chronic kidney disease enrolled few dialysis patients (n = 122 combined). SP rates in a subset of dialysis patients were not reported or not powered to detect statistically significant differences. SP rates in those requiring additional vaccine series or booster doses are not known. METHODS: A retrospective cohort analysis including dialysis patients completing HepB or HepB-CpG vaccination between January 2019 and December 2020. Vaccine-naïve patients received a series of HepB or HepB-CpG (Series 1). A repeat series was given to nonresponders (Series 2). A booster regimen consists of one dose of either vaccine. Primary outcome was achieving SP (anti-HBs >10 mIU/mL) at least 60 days after the last HBV vaccine dose for Series 1 and Series 2, and achieving SP at least 3 weeks post-booster. RESULTS: For Series 1 (n = 3509), SP after HepB vaccination was significantly higher (62.9% versus 50.1% for HepB-CpG; P < 0.0001). Series 2 (n = 1040) and booster (n = 2028) SP rates were similar between vaccines. Patients that received up to four HepB-CpG doses had higher SP rates compared with four doses of HepB (82.0% versus 62.9%, respectively; P < 0.0001). CONCLUSIONS: SP rates in hepatitis B vaccine-naïve dialysis patients administered a recommended four doses of HepB were higher than those recommended two doses of HepB-CpG. SP rates were higher and achieved sooner if HepB-CpG was utilized initially and, if needed, for Series 2. Optimal HepB-CpG dosing deserves further study.

Heplisav-B: A Hepatitis B Vaccine With a Novel Adjuvant.

OBJECTIVE: To review the immunogenicity and safety of a hepatitis B vaccine containing the cytosine phosphoguanosine (CpG) 1018 adjuvant (HepB-CpG). DATA SOURCES: Literature searches were performed using PubMed and Scopus with the search terms hepatitis B vaccine, HepB-CpG, CpG 1018, 1018-ISS, HBsAg-1018, HBV-ISS, and Heplisav. Other sources included the Centers for Disease Control, the Food and Drug Administration, the Advisory Committee on Immunization Practices (ACIP), and prescribing information. STUDY SELECTION AND DATA EXTRACTION: Search limits included randomized controlled trial in humans and published in English from January 2003 to August 2020. Studies using the final formulation and dosing schedule were reviewed. DATA SYNTHESIS: Studies demonstrated that 2 doses of HepB-CpG induced significantly higher seroprotective responses with a faster onset in adults, including those in hyporesponsive populations, compared with 3 doses of alum-adjuvanted Engerix-B. Although the safety profile was comparable to that of Engerix-B, one study observed higher rates of acute myocardial infarction, herpes zoster, and death with HepB-CpG. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: ACIP recommends use of HepB-CpG as an option to prevent hepatitis B virus infection in adults ≥18 years old. Higher immune responses after 2 doses make it a promising option, especially in those with risk factors for hyporesponsiveness or at risk for poor adherence to vaccine series completion. Additional data are needed regarding the vaccine's safety in the general population and the persistence of its antibody response. CONCLUSION: HepB-CpG has been shown to be as immunogenic as Engerix-B; however, long-term safety and persistence of immune memory has yet to be established.

Efficacy of a two-dose hepatitis B vaccination with a novel immunostimulatory sequence adjuvant (Heplisav-B) on patients with chronic liver disease: a retrospective study.

Background: Patients with chronic liver disease (CLD) are more likely to have severe morbidity and mortality due to superimposed acute or chronic hepatitis B virus (HBV) infection and should receive routine vaccination against the virus. Heplisav-B is a two-dose, inactivated, yeast-derived vaccine that uses a novel immunostimulatory adjuvant. Our primary objective was to determine the efficacy of hepatitis B vaccination with Heplisav-B in patients with CLD. Methods: This retrospective cohort analysis included patients ≥18 years old with CLD who received Heplisav-B from January 2018 to January 2021. All patients had anti-HBs <10 IU/L prior to vaccination and received two doses of Heplisav-B. Post-vaccination anti-HBs of ≥10 IU/L was considered successful vaccination. Basic demographic information, laboratory markers, and medical history were collected from the electronic health record. Results: A total of 120 patients were included in analysis. The average age of patients was 59 years, 37% were female, and the most common etiology of liver disease was nonalcoholic fatty liver disease. Median days from 2nd vaccination to post-vaccination HBsAb levels was 121 days. 81/120 (67.5%) of patients had evidence of active immunity after receipt of Heplisav-B. On multivariable analysis, age >50 was associated with reduced odds of successful vaccination (OR =0.19, 95% CI: 0.03-0.76). Conclusions: In patients with CLD, Heplisav-B's overall efficacy (67.5%) is greater than reports of Engerix-B (33-45%), and thus is an effective hepatitis B vaccine in this patient population, particularly in cirrhotic patients. Further studies regarding this vaccine are needed in patients with CLD and after liver transplantation.

Efficacy of Hepatitis B Vaccination with a Novel Immunostimulatory Sequence Adjuvant (Heplisav-B) in Patients With Inflammatory Bowel Disease.

BACKGROUND: Owing to the use of immunosuppressive agents, patients with inflammatory bowel disease (IBD) have an increased risk of vaccine preventable diseases, including infection with hepatitis B virus (HBV). Heplisav-B, an FDA-approved vaccine, is more effective (90% to 100%) than Engerix-B (70.5% to 90.2%) at inducing immunity to HBV in clinical studies. Available data on efficacy of Heplisav-B vaccine in patients with IBD are limited. METHODS: This retrospective observational study included patients age 18 years and older with ulcerative colitis (UC) or Crohn's disease (CD) who received 1 or 2 doses of Heplisav-B vaccine and had postvaccination serologic testing. Prior to immunization, all participants were seronegative for HBsAb antibodies (HBsAb) measured as <10 IU/mL. Postvaccination HBsAb of ≥10 IU/mL was considered successful vaccination. Patient demographics, disease characteristics, and medications were abstracted. RESULTS: One hundred six patients were included in the analysis. Median age was 43 years, and 44 (42%) were female. Thirty-nine patients (37%) had UC, whereas 67 (63%) had CD. Eighty-three patients (78.3%) had active immunity after vaccination with Heplisav-B, with median postvaccination HBsAb levels of 114 IU/L. Patients with chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, immunomodulator use, or those on 2 or more of immunosuppressive medications were less likely to respond to Heplisav-B, though these findings were not statistically significant on a multivariate analysis aside from chronic kidney disease. CONCLUSIONS: Heplisav-B, a 2-dose vaccine, is an effective vaccine for HBV in patients with IBD. In our study, its overall efficacy (78.3%) is greater than that reported for the presently available 3-dose vaccination (Engerix) in patients with IBD.

Heplisav-B, a 2-dose vaccine, is an effective vaccine for HBV in patients with IBD. In our study, it had an overall efficacy of 78.3%. Patients on an immunomodulator and/or 2 or more immunosuppressants had decreased response rate to vaccination.

Seroconversion following Heplisav-B, hepatitis B vaccine (recombinant), adjuvanted, in patients with end-stage renal disease at an urban safety net hospital.

PURPOSE: Heplisav-B is a novel recombinant adjuvanted vaccine for hepatitis B virus (HBV) that has been approved as a 2-dose regimen and shown to have similar seroconversion rates in healthy adults as single-antigen HBV vaccines. More data are needed to determine whether similarly high rates of seroconversion and immunity are observed in immunocompromised patient populations such as in patients with end-stage renal disease (ESRD) on hemodialysis. METHODS: Patients with ESRD who presented for emergency-only hemodialysis and either were HBV vaccine naive or had a hepatitis B surface antibody (anti-HBs) titer of less than 10 IU/mL received 3 standard 20-µg doses of Heplisav-B at week 0, week 4 (±2 weeks), and week 24 (±2 weeks), with anti-HBs titer measured at week 28 (±2 weeks). RESULTS: Thirty-two patients received at least one dose in the study timeframe, with 24 patients completing the vaccine series and measurement of anti-HBs titer. The mean age of the patients was 46 years, and 58% of patients were male. Of the 24 patients who completed the vaccine series, 20 (83%) seroconverted after the third dose. Three of the 4 patients who did not seroconvert after 3 doses were revaccinated with an additional 20-µg dose, and 2 of the 3 patients had an anti-HBs titer of greater than 10 IU/mL 4 weeks after this dose. CONCLUSION: Patients with ESRD who received three 20-µg doses of recombinant HBV vaccine had a seroconversion rate of 83%, representing a similar seroconversion rate and fewer doses of vaccine as compared to the standard HBV vaccine regimen for patients with ESRD.

Hepatitis A and B Vaccination in the United States.

Use of hepatitis A vaccine is a main component of travel vaccination practices. In the United States, fluctuations in the number of annual hepatitis A infections have occurred recently due to large outbreaks related to imported foods and urban transmission among homeless individuals, warranting consideration for wider local use of hepatitis A vaccine. Hepatitis B vaccine is indicated for all adults, and especially healthcare workers. Since 1992, it has been administered at birth. A new novel hepatitis B vaccine given in two doses one month apart is available and has increased efficacy in adults. This article reviews the complete administration of these hepatitis vaccines.

Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults.

BACKGROUND: Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke. METHODS: Phase 3 observer-blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status. RESULTS: Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group. CONCLUSION: Two doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration clinicaltrials.gov Identifier: NCT02117934.

Heplisav-B vaccination for the prevention of hepatitis B virus infection in adults in the United States.

The prevalence of hepatitis B virus (HBV) infections is a worldwide issue that can lead to both acute and chronic complications with increased morbidity and mortality in affected individuals. Current methods of preventing HBV infections primarily include building patient immunity through administration of hepatitis B vaccinations starting at birth. Certain at-risk individuals, including those with occupational exposure to pathogenic bodily fluids, those who are sexually active or intravenous drug users, are recommended to receive some form of hepatitis B vaccination. The current standard of hepatitis B vaccination in the United States is the Engerix-B vaccine, which consists of a three-dose regimen over a 6-month time period. A new hepatitis B vaccine, Heplisav-B, has been approved for adults in the United States and requires only two doses over 1 month. The unique dosing schedule of Heplisav-B provides the potential for increasing patient compliance and therefore can aid in the effort toward protecting individuals from developing an HBV infection. Results from clinical trials showed that Heplisav-B compared favorably with Engerix-B in safety and efficacy profiles. This paper provides a review of the pharmacology, safety, clinical trials and indications for use for the Heplisav-B vaccine in the United States.

Development of the CpG Adjuvant 1018: A Case Study.

The development of aluminum salts (alum) as vaccine adjuvants was an empirical process with little understanding of the mechanism of action and, with decades of use, it has become clear that there is a need for alternatives where alum-based adjuvants are suboptimal. Oligonucleotides containing unmethylated CpG sequences represent one alternative as they are potent stimulators of the vertebrate innate immune system through activation of Toll-like receptor-9. This chapter outlines the methods used by Dynavax Technologies to progress a CpG-containing oligonucleotide sequence termed 1018 through preclinical and clinical testing as an adjuvant for immunization against hepatitis B virus (HBV). 1018 is a short (22-mer) oligonucleotide sequence containing CpG motifs active in both rodents and primates. Preclinical testing of hepatitis B surface antigen (HBsAg) + 1018 in comparison to HBsAg + alum demonstrated induction of substantially higher antibody titers and a favorable safety profile for 1018. Most importantly, clinical studies with HBsAg vaccination consistently demonstrate more rapid induction of protective antibody titers with 1018 compared to alum in all populations studied, including groups that are harder to immunize such as the elderly and immunocompromised individuals. These studies represent the basis for use of the CpG-motif-containing oligonucleotide 1018 as an improved adjuvant for HBsAg immunogenicity. HBsAg + 1018 (HEPLISAV-B™) is currently in late-stage clinical testing for prophylactic immunization against HBV.