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
Sam Jackson, Joseph Lentino, James Kopp, Linda Murray, William Ellison, Margaret Rhee, Gerald Shockey, Lalith Akella, Kimberly Erby, William L Heyward, Robert S Janssen, HBV-23 Study Group, Michael Adams, David Bolshoun, Tami Bruce, Rita Chuang, Donna DeSantis, Thomas Fiel, William Fitzgibbons, David Francyk, Harry Geisberg, Son Giep, Narendra Godbole, Terry Haas, Stephen Halpern, Anthony Inzerello, William Jennings, Scott Kaiser, Jennifer Kay, William Kirby, Robert Lending, Peter Levins, Clifford Molin, Michael Noss, Larry Kotek, Michele Reynolds, Ernie Riffer, Douglas Schumacher, Randall Severance, Royce Solano, Albert Tejada, Leslie Tharenos, Martin Throne, Merle Turner, Thomas Wolf, Mark Woodruff, Sam Jackson, Joseph Lentino, James Kopp, Linda Murray, William Ellison, Margaret Rhee, Gerald Shockey, Lalith Akella, Kimberly Erby, William L Heyward, Robert S Janssen, HBV-23 Study Group, Michael Adams, David Bolshoun, Tami Bruce, Rita Chuang, Donna DeSantis, Thomas Fiel, William Fitzgibbons, David Francyk, Harry Geisberg, Son Giep, Narendra Godbole, Terry Haas, Stephen Halpern, Anthony Inzerello, William Jennings, Scott Kaiser, Jennifer Kay, William Kirby, Robert Lending, Peter Levins, Clifford Molin, Michael Noss, Larry Kotek, Michele Reynolds, Ernie Riffer, Douglas Schumacher, Randall Severance, Royce Solano, Albert Tejada, Leslie Tharenos, Martin Throne, Merle Turner, Thomas Wolf, Mark Woodruff
Abstract
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.
Keywords: Diabetes mellitus; Engerix-B; HEPLISAV-B; Hepatitis B vaccine; Toll-like receptor 9.
Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed