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

Authors: BERTRAN, KATERI - Consultant; KASSA, AEMRO - Boehringer Ingelheim; CRIADO, MIRIA - Consultant; NUNEZ, IVETTE - University Of Georgia; LEE, DONG-HUN - University Of Connecticut; Killmaster, Lindsay; SA E SILVA, MARIANA - Boehringer Ingelheim; ROSS, TED - University Of Georgia; MEBATSION, TESHOME - Boehringer Ingelheim; PRITCHARD, NIKKI - Boehringer Ingelheim; Swayne, David

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2021
Publication Date: 3/11/2021
Citation: Bertran, K., Kassa, A., Criado, M., Nunez, I.A., Lee, D., Killmaster, L.F., Sa E Silva, M., Ross, T.M., Mebatsion, T., Pritchard, N., Swayne, D.E. 2021. 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. Vaccine. 39(14):1933-1942. https://doi.org/10.1016/j.vaccine.2021.02.075.
DOI: https://doi.org/10.1016/j.vaccine.2021.02.075

Interpretive Summary: H5Nx high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong lineage have emerged that are resistant to vaccines. Here, we developed and tested biotechnologically advanced experimental vaccines containing computationally optimized broadly reactive antigen (COBRA) H5 hemagglutinin inserts. In chickens, the COBRA vaccines provided the broadest cross reactivity and neutralization against different H5Nx HPAI field viruses and gave the best protection in chicken vaccine/challenge studies. These COBRA-derived inserts in the recombinant vaccines have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.

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