Joshua DiNapoli
Deputy Director of Viral Immunology, Sanofi Pasteur Biologics LLC,
USA
Title: Universal influenza vaccines: Prevention of infection by matched and mismatched strains
Biography
Biography: Joshua DiNapoli
Abstract
Annual vaccination against seasonal Influenza A and B virus subtypes with well-matched inactivated virus (INV) vaccines are highly effective against upper respiratory tract (URT) Influenza infection and induced disease. Protection against infection is thought to be mediated principally by neutralizing antibodies targeting the receptor binding site (RBS) of the hemagglutinin globular head (HA1). Immune pressure on HA1 results in antigenic drift, necessitating worldwide surveillance with subsequent WHO recommendations on strain selection for manufacture of forthcoming seasonal influenza vaccines. rnrnThe development of Universal Influenza Vaccines (UIV) that could protect against matched as well as drifted or mismatched strains would provide significant improvement over standard of care (SOC). Additionally, a target product profile that also offers long-lasting immunity would be a substantial advantage of current annual vaccination practices, potentially enabling year-round manufacture. UIV that induce both breadth and durability across multiple influenza seasons would be paradigm shifting for the Influenza field and offer significant health care benefits. rnrnAs part of our universal influenza vaccine program, and using the H1 subtype as our proof of concept (POC), we have built consensus-based, computationally optimized broadly reactive antigens (COBRAs). These prototypes have been demonstrated to fold properly, bind conformation-specific mAbs (HA1 & HA2) as well as agglutinate red blood cells. Prototype H1N1 HA proteins were presented on virus-like particles (VLPs), tested in-vivo, and determined to elicit broadly cross-neutralizing functional antibody responses in multiple species and protect against homologous and heterologous virus challenge. This work demonstrates that we can induce broadly-reactive, protective immunity against H1N1 isolates using a consensus-based HA strategy focusing on the globular head, and has important implications for future universal antigen designs.
