Protection of White Leghorn chickens by recombinant fowlpox vector vaccine with updated H5 insert against Mexican H5N2 highly avian influenza viruses

Authors: BERTRAN, KATERI - Consultant; CRIADO, MIRIA FERREIRA - Consultant; LEE, DONG-HUN - Orise Fellow; Killmaster, Lindsay; SA-E-SILVA, MARIANA - Boehringer Ingelheim; LUCIO, EDUARDO - Boehringer Ingelheim; WIDENER, JUSTIN - Boehringer Ingelheim; PRITCHARD, NIKKI - Boehringer Ingelheim; ATKINS, EMILY - Boehringer Ingelheim; MEBATSION, TESHOME - Boehringer Ingelheim; Swayne, David

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/25/2019
Publication Date: 12/18/2019
Citation: Bertran, K., Criado, M., Lee, D., Killmaster, L.F., Sa-E-Silva, M., Lucio, E., Widener, J., Pritchard, N., Atkins, E., Mebatsion, T., Swayne, D.E. 2019. Protection of White Leghorn chickens by recombinant fowlpox vector vaccine with updated H5 insert against Mexican H5N2 highly avian influenza viruses. Vaccine. 38(6):1526-1534. https://doi.org/10.1016/j.vaccine.2019.11.072.
DOI: https://doi.org/10.1016/j.vaccine.2019.11.072

Interpretive Summary: Despite decades of vaccination, surveillance, and biosecurity measures, H5N2 avian influenza virus (AIV) infections continue in Mexico and other neighboring countries. We analyzed the genome sequences of circulating H5N2 field viruses and the vaccines used to date. Our analyzes showed that the vaccine should be updated to protect against newly circulating H5N2 AIVs in Mexico. In addition, we tested a new recombinant vaccine (H5/2016) in chickens which provided 100% protection from H5N2 low and highly pathogenicity AIV and is a good candidate in vaccination program against new H5N2 AIVs in Mexico.

Technical Abstract: Despite decades of vaccination, surveillance, and biosecurity measures, H5N2 low pathogenicity avian influenza (LPAI) virus infections continue in Mexico and neighboring countries. One explanation for tenacity of H5N2 LPAI in Mexico is the antigenic divergence of circulating field viruses compared to licensed vaccines due to antigenic drift. Our phylogenetic analysis indicates that the H5N2 LPAI viruses circulating in Mexico and neighboring countries since 1994 have undergone antigenic drift away from vaccine seed strains. Here we evaluated the efficacy of a new recombinant fowlpox virus vector containing an updated H5 insert (rFPV-H5/2016), more relevant to the current strains circulating in Mexico. We tested the vaccine efficacy against a closely related subcluster 4 Mexican H5N2 LPAI (2010 H5/LP) virus and the historic H5N2 HPAI (1995 H5/HP) virus in White Leghorn chickens. The rFPV-H5/2016 vaccine provided hemagglutinin inhibition (HI) titers pre-challenge against viral antigens from both challenge viruses in almost 100% of the immunized birds, with no differences in number of birds seroconverting or HI titers among all tested doses (1.5, 2.0, and 3.1 log10 mean tissue culture infectious doses/bird). The vaccine conferred 100% clinical protection and a significant decrease in oral and cloacal virus shedding from 1995 H5/HP virus challenged birds when compared to the sham controls at all tested doses. Virus shedding titers from vaccinated 2010 H5/LP virus challenged birds significantly decreased compared to sham birds especially at earlier time points. Our results confirm the efficacy of the new rFPV-H5/2016 against antigenic drift of LPAI virus in Mexico and suggest that this vaccine would be a good candidate, likely as a primer in a prime-boost vaccination program.