Evaluation of immune response in calves vaccinated with baculovirus vectored inactivated vaccine expressing 2.3.4.4b H5 protein of highly pathogenic Avian Influenza virus

Clade 2.3.4.4b H5N1 highly pathogenic avian influenza (HPAI) virus is circulating widely in US dairy cattle with significant implications for milk production and cow health. Due to the critical need for intervention strategies for continuing outbreaks of bovine HPAI, a baculovirus vectored inactivated HPAI vaccine expressing the 2.3.4.4b H5 protein (Avian Influenza-H5) was developed utilizing a licensed prescription platform which has been tested and proven safe in multiple species. The immunogenicity of recombinant Avian Influenza-H5 vaccine was tested in 5-month-old calves. The subcutaneously vaccinated animals showed minor post-injection site swelling that resolved without further affect (or compromise). The vaccine induced a measurable immune response by ELISA 3 weeks after 1st vaccination although the antibody response was low or undetectable by virus neutralization (VN) or hemagglutination inhibition (HI) tests. Two- and four weeks after a 2nd vaccination, antibody titers greater than > 40, which are typically considered minimum protective titer against HPAI virus challenge, were consistently observed in all the vaccinated animals by both HI and VN tests. Strong correlation between VN and HI titers (Pearson correlation coefficient (r) greater than 0.8) were observed. Because the vaccine only contains the H5 protein of influenza virus, all vaccinated animals were negative against nucleoprotein (NP) and N1 neuraminidase antibody by commercial NP ELISA and N1 specific enzyme linked lectin assay, respectively, which confirm the vaccine is DIVA (differentiation of infected from vaccinated) surveillance compatible. In summary, this study demonstrates that an inactivated baculovirus-vectored vaccine, Avian Influenza-H5, is immunogenic and generates presumed protective antibody levels in calves, although future studies evaluating the vaccine in lactating dairy cattle would determine the induction of local immunity in the mammary gland and milk, and if the vaccine provides field protection against influenza-induced mastitis.