Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage emergence vaccine-resistant field underscores need for a broadly protective H5 A vaccine. Here, we tested experimental vector herpesvirus turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived inserts or computationally optimized reactive antigen (COBRA) challenge by homologous genetically divergent HPAI Gs/GD in chickens. Direct assessment protection was confirmed all constructs, which provided clinical against heterologous significantly decreased oropharyngeal shedding titers compared to sham cross reactivity assessed hemagglutinin inhibition (HI) focus reduction assay panel phylogenetically antigenically diverse strains. COBRA-derived elicited antibody responses strains, while wild-type-derived mostly close related clades 2.3.4.4A 2.3.4.4D viruses. In conclusion, HVT vector, widely used replicating vaccine platform poultry, insert provides significant viral challenge. addition, have potential be distinct co-circulating future variants.