A computationally designed H5 antigen shows immunological breadth of coverage and protects against drifting avian strains

Authors: ROSS, TED - University Of Georgia; DINAPOLI, JOSHUA - Sanofi Pasteur Biologics Co; GEIL-MOLONEY, MARYANN - Sanofi Pasteur Biologics Co; BLOOM, CHALISE - University Of Georgia; BERTRAN, KATERI - Consultant; Balzli, Charles; STRUGNELL, TOD - Sanofi Pasteur Biologics Co; SA E SILVA, MARIANA - Merial, Ltd; MEBATSION, TESHOME - Merial, Ltd; BUBLOT, MICHEL - Merial Sas Research & Development; Swayne, David; KLEANTHOUS, HARRY - Sanofi Pasteur Biologics Co

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/11/2019
Publication Date: 3/21/2019
Publication URL: https://handle.nal.usda.gov/10113/6338104
Citation: Ross, T.M., Dinapoli, J., Geil-Moloney, M., Bloom, C.E., Bertran, K., Balzli, C.L., Strugnell, T., Sa E Silva, M., Mebatsion, T., Bublot, M., Swayne, D.E., Kleanthous, H. 2019. A computationally designed H5 antigen shows immunological breadth of coverage and protects against drifting avian strains. Proceedings of the National Academy of Sciences. 37:2369-2376. https://doi.org/10.1016/j.vaccine.2019.03.018.
DOI: https://doi.org/10.1016/j.vaccine.2019.03.018

Interpretive Summary: Since the first identification of the H5N1 highly pathogenic avian influenza virus (HPAIV) in domestic geese in China during 1996, this virus has spread worldwide with occasional human infections and highlights the need for a broadly protective H5 influenza vaccine in case of a pandemic. In this study, we developed and tested two computationally optimized broadly reactive antigen (COBRA), for a novel hemagglutinin (HA) based vaccine. The COBRA-2 HA vaccine produced seroprotective antibody responses against genetically diverse genetic groups of H5 HPAIVs and protected chickens against a recent drifted variant. The computer optimized vaccine design strategy worked .

Technical Abstract: Since the first identification of the H5N1 Goose/Guangdong lineage in birds in 1996, this highly pathogenic avian influenza virus has spread worldwide becoming endemic in domestic poultry. Sporadic transmission to humans has raised concerns of a potential pandemic and underscores the need for a broad cross-protective influenza vaccine. In this study, we tested our previously described methodology termed computationally optimized broadly reactive antigen (COBRA), to generate a novel hemagglutinin (HA) gene, termed COBRA-2, that was based on H5 HA sequences from 2005-2006. The COBRA-2 HA virus-like particle (VLP) vaccines were used to vaccinate chickens and the immune responses were compared to responses elicited by VLP’s expressing HA from A/Whooper Swan/Mongolia/244/2005 (WS/05), a representative 2005 vaccine virus from clade 2.2. To support this evaluation a hemagglutination inhibition (HAI) breadth panel was developed consisting of phylogenetically and antigenically diverse H5 strains in circulation from 2005 – 2006, as well as recent drift variants (2008 – 2014). We found that the COBRA-2 VLP vaccines elicited robust HAI titers against this entire breadth panel, whereas the VLP vaccine based upon the recommended WS/05 HA only elicited HAI responses against a subset of these strains. Furthermore, while all vaccines protected chickens against challenge with the WS/05 virus, only the human COBRA-2 VLP vaccinated birds were protected (80%) against a recent drifted clade 2.3.2.1B, A/Duck/Vietnam/NCVD-672/2011 (VN/11) virus. This is the first report to demonstrate seroprotective antibody responses against genetically diverse clades and sub-clades of H5 viruses and protective efficacy against a recent drifted variant using a globular head based design strategy.