|CRIADO, MIRIA - Consultant|
|BERTRAN, KATERI - Consultant|
|LEE, DONG-HUN - Orise Fellow|
|STEPHENS, CHRISTOPHER - Orise Fellow|
|ATKINS, EMILY - Boehringer Ingelheim|
|SA E SILVA, MARIANA - Boehringer Ingelheim|
|MEBASTSION, TESHOME - Boehringer Ingelheim|
|SMITH, ROBERT - Boehringer Ingelheim|
|HUGHES, TROY - Boehringer Ingelheim|
|WIDENER, JUSTIN - Boehringer Ingelheim|
|PRITCHARD, NIKKI - Boehringer Ingelheim|
Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/3/2019
Publication Date: 4/10/2019
Publication URL: http://handle.nal.usda.gov/10113/6338095
Citation: Criado, M.F., Bertran, K., Lee, D., Killmaster, L.F., Stephens, C.B., Spackman, E., Atkins, E., Sa E Silva, M., Mebastsion, T., Smith, R., Hughes, T., Widener, J., Pritchard, N., Swayne, D.E. 2019. Efficacy of novel recombinant fowlpox vaccine against recent Mexican H7N3 highly pathogenic avian influenza virus. Vaccine. 37(16):2232-2243. https://doi.org/10.1016/j.vaccine.2019.03.009.
Interpretive Summary: Highly pathogenic avian influenza (H7N3 HPAIV) outbreaks have been occurring in Mexico since 2012, affecting millions of poultry, but recently, outbreaks of disease have been reported in vaccinated chickens. We studied why the vaccines failed. Three weeks after vaccination of chickens, a new vaccine provided 100% protection from a 2015 Mexican H7N3 HPAI virus. However, the old vaccine which protected against a 2012 Mexican H7N3 HPAI virus, did not protect against a 2015 Mexican H7N3 HPAIV. An increase in sugar molecules on the hemagglutinin surface protein on the 2015 Mexican H7N3 HPAI virus was responsible for the loss of vaccine induced protection.
Technical Abstract: Since 2012, H7N3 highly pathogenic avian influenza (HPAI) has had negative economic and animal welfare impacts on poultry in central Mexico. In the present study, chickens were vaccinated with two different recombinant fowlpox virus vaccine (rFPV-H7/3002 with 2015 H7 hemagglutinin [HA] gene insert, and rFPV-H7/2155 with 2002 H7 HA gene insert), and were then subsequently challenged with H7N3 HPAI virus (A/chicken/Jalisco/CPA-37905/2015). The rFPV-H7/3002 vaccine conferred 100% protection against mortality and morbidity, and significantly reduced virus shed titers from the respiratory and gastrointestinal tracts. In contrast, 100% of sham and rFPV-H7/2155 vaccinated birds shed virus at higher titers and died within 4 days. Pre- (15/20) and post- (20/20) challenge serum of birds vaccinated with rFPV-H7/3002 had antibodies detectable by hemagglutination inhibition (HI) assay. However, only a few birds (3/20) in the rFPV-H7/2155 vaccinated group had antibodies that reacted against the challenge strain but a high number of birds had antibodies that reacted against the homologous vaccine antigen (A/turkey/Virginia/SEP-66/2002) (20/20). As an explanation of reduced serological reaction and protection, we identified in silico three potential new N-glycosylation sites on the globular head of the H7 HA of A/chicken/Jalisco/CPA-37905/2015 challenge virus, which were absent in 2012 H7N3 outbreak virus. The presence of additional N-linked glycans in the H7 HA was confirmed by PNGase F digestion and western blot analysis. This study confirms the importance of frequent updating of vaccines seed strains for long-term effective control of H7 HPAI virus.