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. 2021 Apr 1;39(14):1933-1942. doi: 10.1016/j.vaccine.2021.02.075. Epub 2021 Mar 11.

Abstract

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) 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 clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) 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.

Keywords: Avian influenza; COBRA; H5; HPAIV; HVT recombinant vector vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • Chickens
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinins
  • Influenza A Virus, H5N1 Subtype* / genetics
  • Influenza Vaccines*
  • Influenza in Birds* / prevention & control
  • Marek Disease* / prevention & control
  • Vaccines, Synthetic / genetics
  • Virulence

Substances

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Influenza Vaccines
  • Vaccines, Synthetic