Efficacy of novel recombinant fowlpox vaccine against recent Mexican H7N3 highly pathogenic avian influenza virus |
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Authors: | Miria Ferreira Criado Kateri Bertran Dong-Hun Lee Lindsay Killmaster Christopher B. Stephens Erica Spackman Mariana Sa e Silva Emily Atkins Teshome Mebatsion Justin Widener Nikki Pritchard Hallie King David E. Swayne |
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Affiliation: | 1. Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, Athens, GA, USA;2. Boehringer Ingelheim Animal Health, Athens, GA 30601, USA;3. Boehringer Ingelheim Animal Health, Gainesville, GA 30503, USA |
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Abstract: | Since 2012, H7N3 highly pathogenic avian influenza (HPAI) has produced negative economic and animal welfare impacts on poultry in central Mexico. In the present study, chickens were vaccinated with two different recombinant fowlpox virus vaccines (rFPV-H7/3002 with 2015 H7 hemagglutinin [HA] gene insert, and rFPV-H7/2155 with 2002 H7 HA gene insert), and were then challenged three weeks later 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 using challenge virus antigen. However, only a few birds (3/20) in the rFPV-H7/2155 vaccinated group had antibodies that reacted against the challenge strain but all birds had antibodies that reacted against the homologous vaccine antigen (A/turkey/Virginia/SEP-66/2002) (20/20). One possible explanation for differences in vaccines efficacy is the antigenic drift between circulating viruses and vaccines. Molecular analysis demonstrated that the Mexican H7N3 strains have continued to rapidly evolve since 2012. In addition, 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. Our results suggested that mutations in the HA antigenic sites including increased glycosylation sites, accumulated in the new circulating Mexican H7 HPAIV strains, altered the recognition of neutralizing antibodies from the older vaccine strain rFPV-H7/2155. Therefore, the protective efficacy of novel rFPV-H7/3002 against recent outbreak Mexican H7N3 HPAIV confirms the importance of frequent updating of vaccines seed strains for long-term effective control of H7 HPAI virus. |
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Keywords: | Chickens High pathogenicity avian influenza H7N3 Immunity Recombinant fowlpox virus vaccine Vaccine Jalisco/12283/2012 A/chicken/Jalisco/CPA-12283/2012 [H7N3] Jalisco/37905/2015 A/chicken/Jalisco/CPA-37905/2015 [H7N3] AP Alkaline phosphatase ABSL-2 Animal biosafety level 2 ABSL-3E Animal biosafety level 3 enhanced AIV Avian influenza viruses CL Cloacal swabs dpc Days post-challenge DI Defective interfering ECE Embryonating chicken eggs 50 percent embryo infectious doses GMT Geometric mean titers HI Hemagglutination inhibition HA Hemagglutinin HPAI Highly pathogenic avian influenza LPAI Low pathogenicity avian influenza MDT Mean death time NA Neuraminidase OP Oropharyngeal swabs qRRT-PCR Quantitative real-time RT-PCR SDS-PAGE SDS-polyacrylamide gel electrophoresis SEPRL Southeast Poultry Research Laboratory SPF Specific-pathogen-free SQ Subcutaneous TBST Tris-buffered saline with Tween 20 WL White Leghorn |
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