作者: Atsmon, Jacob ; Yayon-Gur, Vered ; Spaans, Johanna N ; Sabbah, Cyril ; Yassin-Rajkumar, Bebi ; Popovic, Vlad ; Anderson, David E ; Machluf, Nathalie ; Diaz-Mitoma, Francisco

BACKGROUNDSci-B-Vac® is a tri-antigenic recombinant Hepatitis B vaccine (TAV) containing the small (s), medium (pre-S2) and large (pre-S1) hepatitis B surface (HBs) antigens. To comply with vaccine licensure, a new reference standard batch was qualified by characterizing the seroprotection rate (SPR) for anti-HBs titers ≥10 mIU/mL, following vaccination.METHODSNinety-one healthy adults aged 20-40 years were enrolled in an open label, single-arm phase IV study receiving three IM doses of 10 μg TAV at 0, 1 and 6 months. Immunogenicity was evaluated monthly and at 7, 9 and 12 months. The primary endpoint to qualify the reference standard was an SPR ≥95% by month 7. Secondary endpoints were proportion of high responders (anti-HBs titers ≥100 mIU/mL) and geometric mean concentrations (GMC) of HBs antibodies each month. Participants were followed for safety to month 12.RESULTSThe primary endpoint was met 2 months after the second dose at month 3 [SPR 98.8%; 95% CI: 93.7%, 99.7%]. Proportion of high responders at months 3 and 7 were 81.4% and 97.6%, respectively. GMC at months 3 and 7 were 413.6 mIU/mL and 6799.9 mIU/mL, respectively. TAV was safe and well-tolerated.CONCLUSIONSThe new reference standard batch of TAV was qualified successfully, demonstrating efficacy, a favorable safety profile and a rapid onset of seroprotection, including after two vaccine doses. Clinical trial registry: NCT04179786.

2020-12-31·Open Forum Infectious Diseases

1051. Rapid onset of seroprotection rates in young adults immunized with a tri-antigenic hepatitis B virus (HBV) vaccine compared to a mono-antigenic HBV vaccine

作者: Popovic, Vlad ; Vesikari, Timo ; Langley, Joanne M ; Machluf, Nathalie ; Anderson, Dave ; Spaans, Johanna ; Yassin-Rajkumar, Bebi ; Diaz-Mitoma, Francisco

AbstractBackgroundHepatitis B (HBV) remains a significant public health risk with an estimated 240-350 million people chronically-infected with HBV worldwide. In the US, rates of new HBV infections are highest among individuals aged 30-39 years, highlighting the elevated risk in adults. Moreover, CDC reported that in 2017 only 34.3% of US adults aged 19-49 years were vaccinated against HBV. Younger adults who are at-risk of HBV infection, through exposure in the workplace or home (e.g. healthcare workers, public service sector workers, those living with HBsAb-positive individuals), through travel to countries with high HBV prevalence, or through exposure as a result of high-risk behavior (e.g. injection drug use, risk through sexual transmission), need a highly effective and safe HBV vaccine with a rapid onset of seroprotection.Seroprotection Rates from Phase 3 StudiesMethodsFour phase 3 studies assessing kinetics of seroprotection rates (SPR; anti-HBs ≥ 10 mIU/mL) in adults aged 18-45 years, vaccinated at months 0, 1 and 6 with 10 µg of tri-antigenic HBV vaccine (TAV) vs. 20 µg of a mono-antigenic HBV vaccine (MAV) were completed between 2008 & 2020: (1) PROTECT study in US, Europe, and Canada, n = 299; (2) CONSTANT study in US, Europe and Canada, n = 2,838; (3) SG-005-05 study in Vietnam, n = 349; (4) 38-13-040 study in Russia, n = 99. One phase 4, single-arm study was conducted with 10 µg of TAV in adults aged 20-40 years: SciB018 study in Israel, n = 83.ResultsIn all five studies, vaccination with TAV achieved SPRs of 87.2-100.0% at month 6 after 2 doses and 99.2-100.0% at month 7 after 3 doses, compared to 39.0-89.4% and 91.1-98.3% achieved with MAV at months 6 and 7, respectively (Fig 1). Moreover, as demonstrated with the data available from two of the controlled studies, TAV induced SPRs of 76.0%-95.9% at month 3 after 2 doses compared to 37.2%-87.2% with MAV. No major safety signals were observed, and adverse events were well-balanced and consistent with the known vaccine safety profiles.ConclusionTri-antigenic HBV vaccine (TAV) has demonstrated its ability to rapidly, consistently, and safely elicit high SPRs in younger adults across different regions of the world.DisclosuresJoanne M. Langley, MD, GSK group of companies (Research Grant or Support)Immunivaccines Inc (Scientific Research Study Investigator, Research Grant or Support)Janssen (Research Grant or Support)Pfizer (Research Grant or Support)Symvivo (Scientific Research Study Investigator, Research Grant or Support)VBI Vaccines (Research Grant or Support) Nathalie Machluf, PhD, VBI Vaccines Inc. (Employee) Johanna Spaans, BSc, MSc, VBI Vaccines Inc (Employee) Dave Anderson, PhD, VBI Vaccines (Employee, Shareholder) Vlad Popovic, MD, VBI Vaccines, Inc. (Employee, Shareholder) Francisco Diaz-Mitoma, MD, VBI Vaccines, Inc. (Shareholder, Independent Contractor)

2020-12-31·Open Forum Infectious Diseases

8. Higher hepatitis B antibody titres induced in all adults vaccinated with a tri-antigenic hepatitis B (HBV) vaccine, compared to a mono-antigenic HBV vaccine: results from two pivotal phase 3 double-blind, randomized studies (PROTECT and CONSTANT)

作者: Vesikari, Timo ; Popovic, Vlad ; Anderson, Dave ; Langley, Joanne M ; Machluf, Nathalie ; Spaans, Johanna ; Yassin-Rajkumar, Bebi ; Diaz-Mitoma, Francisco

AbstractBackgroundMore than 2 billion individuals worldwide have evidence of past or current hepatitis B virus (HBV) infection, emphasizing the importance of awareness and need for elimination of HBV infection. Effective vaccination, defined as the induction of protective anti-HBs titres, is a key component of those elimination plans. Magnitude of the immune response to HBV vaccines can be measured by serum levels of anti-HBs, whose persistence and durability is believed to be dependent upon the peak antibody levels reached after completion of vaccinations.CONSTANT and PROTECT: High Hepatitis B antibody titres after vaccinationMethodsIn two phase 3, head-to-head studies of immunogenicity and safety of a tri-antigenic HBV vaccine (TAV) containing 10 µg of full-length HBs (pre-S1 + pre-S2 + S antigens) and a mono-antigenic HBV vaccine (MAV) containing 20 µg of small HBs antigen, subjects were vaccinated at months 0, 1 and 6 with safety follow-up for at least 6 months after the 3rd vaccination. PROTECT, which enrolled 1607 adults age ≥18, demonstrated non-inferiority of seroprotection rates (SPR, defined as the % of participants achieving anti-HBs titres ≥10 mIU/mL) of TAV vs. MAV in adults age ≥ 18 and superiority of SPR in adults age ≥ 45. CONSTANT, which enrolled 2838 adults age 18–45 demonstrated manufacturing equivalence of 3 lots of TAV. In both studies, anti-HBs titres were measured across timepoints and safety was assessed.ResultsIn CONSTANT, at day 168 after two doses, mean anti-HBs titers (mIU/mL) induced across the 3 lots of TAV were > 7.5x those induced with MAV [113–124 vs. 15]. At day 196, after the 3rd dose, mean anti-HBs titers induced with TAV remained substantially higher than those induced with MAV [4855–5979 vs. 1526] (Fig A). In PROTECT, anti-HBs titers were 6x higher in all subjects ≥ 18 year at day 196 [1148 vs. 193] with TAV and 5-8x higher in key subgroups compared to MAV, regardless of age, BMI, or diabetic status (Fig B). Adverse events were well-balanced and consistent with known vaccine safety profiles.ConclusionIn the two pivotal phase 3 studies, TAV demonstrated its ability to rapidly elicit higher anti-HBs titres compared to MAV, in all study subject populations, reflecting the very strong immune response to TAV, which may be an important predictor of the persistence and durability of seroprotection.DisclosuresJoanne M. Langley, MD, GSK group of companies (Research Grant or Support)Immunivaccines Inc (Scientific Research Study Investigator, Research Grant or Support)Janssen (Research Grant or Support)Pfizer (Research Grant or Support)Symvivo (Scientific Research Study Investigator, Research Grant or Support)VBI Vaccines (Research Grant or Support) Nathalie Machluf, PhD, VBI Vaccines Inc. (Employee) Johanna Spaans, BSc, MSc, VBI Vaccines Inc (Employee) Dave Anderson, PhD, VBI Vaccines (Employee, Shareholder) Vlad Popovic, MD, VBI Vaccines, Inc. (Employee, Shareholder) Francisco Diaz-Mitoma, MD, VBI Vaccines, Inc. (Shareholder, Independent Contractor)

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