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)
Authors: Langley Joanne M , Vesikari Timo , Machluf Nathalie , Spaans Johanna , Yassin-Rajkumar Bebi , Anderson Dave , Popovic Vlad , Diaz-Mitoma Francisco 
Published: January 2021

Abstract

Background
More 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 vaccination

Methods
In 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.

Results
In CONSTANT, at day 168 after two doses, mean anti-HBs titers (mIU/mL) induced across the 3 lots of TAV were &gt; 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.

Conclusion
In 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.

Disclosures
Joanne 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)