Biography
Biography: Rainer Henning
Abstract
Background: HBV infection remains a serious global health challenge. 5-10% of vaccines with available vaccines do not achieve seroconversion. 350 million patients worldwide live with chronic HBV infections. New vaccine designs are required to tackle these important challenges.
Aim: Characterization of the protective effect of HBV PreS fusion proteins contained in the clinical stage allergy vaccine BM32 with respect to protection against infection with HBV.
Methods: Epitope mapping of the antibody response elicited by BM32 in rabbits and patients was performed using a collection of overlapping 30-mer peptides derived from PreS1. The sera from these animals and patients were also tested for their ability to protect HepG2-NTCP cells against infection in cell culture. Outcome measures were the secretion of HBsAg and expression of HBeAg.
Results: Sera from patients and animals immunized with BM32 demonstrated selectivity towards the NTCP binding site of the large HBV surface antigen. The selectivity was stronger in humans than in rabbits. These sera protect HepG2-NTCP cells from HBV infection to a similar extent as sera from subjects vaccinated with Engerix- B. The anti HBV activity in BM32 resides predominantly in one fusion protein component, which will be developed as VVX001.
Conclusion: BM32, containing fusion proteins with PreS from HBV capped with peptides at both termini elicits a neutralizing IgG antibody response in immunized individuals. This immune response is focused on the virus attachment site and prevents virus entry into target cells. One of the components of BM32 is responsible for this effect and may be a promising HBV vaccine candidate.
