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

Ted M. Ross, Joshua DiNapoli, Maryann Giel-Moloney, Chalise E. Bloom, Kateri Bertran, Charles Balzli, Tod Strugnell, Mariana Sá e Silva, Teshome Mebatsion, Michel Bublot, David E. Swayne, Harry Kleanthous
Vaccine 2019 v.37 no.17 pp. 2369-2376
Influenza A virus, antibodies, antigens, chickens, ducks, genes, hemagglutination, hemagglutinins, humans, influenza vaccines, pandemic, phylogeny, swans, virus-like particle vaccines, viruses
Since the first identification of the H5N1 Goose/Guangdong lineage 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. Here, 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 to 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 to 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 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, 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.