Development of VSV-vector based vaccine against H5N1 avian influenza by targeting both H5N1 hemagglutinin and matrix protein 2

Title : Development of VSV-vector based vaccine against H5N1 avian influenza by targeting both H5N1 hemagglutinin and matrix protein 2

Abstract:

Human (avian) influenza A viruses, especially highly pathogenic avian influenza (HPAI) viruses, pose a significant public health threat, and a multivalent vaccine is the primary prophylactic measure to control these viruses. To this goal, we generated two vesicular stomatitis virus (VSV)-based vaccine candidates simultaneously targeting H5N1 hemagglutinin (HA) and matrix protein 2 (M2) (V-EtM2e/H5₀₅ and V-EtM2e/H5₂₂) and characterized their ability to induce protective immune responses. Our results revealed that vaccine immunization induced high humoral immune responses against both the HPAI HA protein and the ectodomain of M2 protein in mice. Intriguingly, vaccine-immunized mice sera exhibited highly efficient neutralizing activity against the corresponding H5 pseudovirus and mediated potent and broad antibody-dependent cellular cytotoxicity (ADCC) activity against M2e derived from human and avian influenza H5, H1, H3, and H7 viruses. Furthermore, both intranasal (IN) and intramuscular (IM) immunization provided efficient protection against HPAI H5N1 virus challenge in mice, with a 100% survival rate and a nondetectable viral load in several tissues. Notably, noninvasive mucosal delivery of V-EtM2e/H5₂₂ achieved protection equal to that of IM delivery at a 100-fold lower immunizing dose. These findings provide convincing evidence for the high efficiency of a multivalent VSV-based vaccine against human (avian) influenza A viruses.

Biography:

Dr. Zhujun Ao obtained her M.D. and PhD. degrees respectively at Zunyi Medical University and at the University of Montreal. Since 2007, she has been working as Postdoc Fellow, Research Associate at the Laboratory of Molecular Human Retrovirology, in the Department of Medical Microbiology, University of Manitoba. Dr. Zhujun Ao’s research projects have been in the fundamental research to explore HIV and host protein interactions and their functional roles during HIV-1 replication, and to develop new approaches against HIV-1. Recent 5 years, she has been the Lead Research Associate working on the development of vaccines, particularly with respect to HIV, SARS-Cov2 and influenza viral infections. Until now, she has published more than 60 peer-reviewed scientific papers and was the Recipient of New Investigator Award (2005) and Mark Wainberg Fund Grant (2023) of the Annual Canadian Conference on HIV/AIDS Research/Canadian Institutes of Health Research.