Poster Presentation Lorne Infection and Immunity 2022

Targeted HBeAg seroclearance in a chronic-like HBV mouse model using chimeric bionanoparticles. (#139)

Yianni Droungas 1 2 , Hugh Mason 2 , Chee Leng Lee 2 , Joan Ho 2 , Rachel Hammond 2 , Stephen Locarnini 2 , Renae Walsh 2 , Hans J Netter 2 3 , Peter A Revill 2
  1. Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  2. Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  3. Royal Melbourne Institute of Technology (RMIT) University, Melbourne, VIC, Australia

Introduction: Chronic hepatitis B (CHB) contributes to more than 880,000 deaths each year, and despite existing prophylactic and therapeutic advances, there is currently no cure. An important viral protein, the hepatitis B e antigen (HBeAg) is essential for initial establishment of CHB by modulating the host’s immune responses. HBeAg seroconversion is a current treatment endpoint and a preceding step for functional cure. This project utilises HBeAg-epitope expressing bio-nanoparticles (eBNPs) to program the immune responses for detection and clearance of HBeAg at earlier phases of infection, as a groundwork step towards a potential novel curative approach.

Methods: Our bionanoparticles are non-infectious, sub-viral particles composed of the HBsAg, making excellent presentation platforms by providing high antigenic density of exposed epitopes. In this project, eBNPs candidates were bioengineered and characterised against the epitopes of interest. Then, the most immunogenic eBNP candidates were used to challenge a chronic-like HBV mouse model and stimulate immune responses against HBeAg and HBsAg.

Results: In this project, biochemical characterisation of eBNPs has demonstrated their immunogenic against the inserted HBeAg epitopes whilst also maintaining some immunogenicity against the HBsAg backbone protein. Challenging a chronic-like HBV mouse model with eBNPs resulted in seroclearance of HBeAg in 43% of eBNP3 group (3/7 mice) and 67% of eBNP6 group (8/12 mice). In addition, 17% of eBNP6 group (2/12 mice) serocleared HBsAg, achieving functional cure.

Discussion: The immune factors contributing to HBeAg seroconversion in CHB patients remain unclear. This project is the first to describe assembly-competent, immunogenic eBNPs capable to selectively trigger immune responses against the native HBeAg and induce its seroclearance. The successful production of eBNPs forms the basis of initiating a novel experimental approach to target HBeAg, further investigate the immune factors contributing to its seroclearance and progress towards a potential curative outcome.