Skip to main content
ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Exotic & Emerging Avian Viral Diseases Research » Research » Publications at this Location » Publication #313816
Title: A computationally optimized broadly reactive H5 hemagglutinin vaccine provides protection against homologous and heterologous H5N1 highly pathogenic avian influenza virus infection in chickens

Author
item BERTRAN, KATERI - Consultant
item Balzli, Charles
item SA E SILVA, MARIANA - Former ARS Employee
item Moresco, Kira
item ROSS, TED - Vaccine & Gene Therapy Institute Of Florida
item BLOOM, CHALISE - Vaccine & Gene Therapy Institute Of Florida
item BUBLOT, MICHEL - Merial Sas Research & Development
item PRITCHARD, NIKKI - Merial, Ltd
item MEBATSION, TESHOME - Merial, Ltd
item DINAPOLI, JOSHUA - Sanofi-Aventis Us, Inc
item VOGEL, THORSTEN - Sanofi-Aventis Us, Inc
item ALEFANTIS, TIM - Sanofi-Aventis Us, Inc
item KLEANTHOUS, HAROLD - Sanofi-Aventis Us, Inc
item Swayne, David

Submitted to: World Veterinary Poultry Association
Publication Type: Abstract Only
Publication Acceptance Date: 3/1/2015
Publication Date: 9/7/2015
Citation: Bertran, K., Balzli, C.L., Sa E Silva, M., Moresco, K.A., Ross, T.M., Bloom, C.E., Bublot, M., Pritchard, N., Mebatsion, T., Dinapoli, J., Vogel, T., Alefantis, T., Kleanthous, H., Swayne, D.E. 2015. A computationally optimized broadly reactive H5 hemagglutinin vaccine provides protection against homologous and heterologous H5N1 highly pathogenic avian influenza virus infection in chickens [abstract]. Abstracts of the International Congress of the World Veterinary Poultry Association. CDROM.

Interpretive Summary:

Technical Abstract: Since its emergence in 1996 in China, H5N1 highly pathogenic avian influenza (HPAI) virus has continuously evolved into different genetic clades that have created challenges to maintaining antigenically relevant H5N1 vaccine seeds. Therefore, a universal (multi-hemagglutinin [HA] subtype) or more cross-protective H5 subtype vaccine is needed. In this study, we generated two synthetic H5 HA vaccines utilizing computationally optimized broadly reactive antigens (COBRA). Chickens were immunized at 3 and 5 weeks with human and avian COBRA HA H5N1 virus-like particles (VLP) (H5-COBRA-1-VLP); human COBRA HA H5N1 VLP (H5-COBRA-2-VLP); A/Whooper swan/Mongolia/244/2005 HA H5N1 VLP (WS/05-VLP); sequential cH6/1 and cH9/1 chimeric HAs; or sham immunization. The positive vaccine control was single dose, inactivated WS/05 vaccine (WS/05-killed). For each vaccination regime, chickens were challenged at 7 weeks with either homologous WS/05 or heterologous A/duck/Vietnam/NCVD-672/2011 isolates. Sham and chimeric HA vaccinated chickens experienced 100% mortality, with similar mean death times (MDTs) ranging 2.2-2.7 days post-challenge (dpc). H5-COBRA-1-VLP, H5-COBRA-2-VLP, WS/05-VLP, and WS/05-killed vaccine regimes conferred 100% clinical protection against homologous WS/05 challenge. Heterologous challenge caused 100% mortality in H5-COBRA-1-VLP and WS/05-VLP immunized chickens, with slightly delayed MDTs (4.5 and 5.1 dpc, respectively), while WS/05-killed experienced intermediate (33%) mortality, and H5-COBRA-2-VLP good (80%) protection. None of the vaccine regimes significantly reduced the number of birds shedding, but all except chimeric HAs significantly reduced shed viral titers compared to the sham groups. The COBRA HA H5N1 VLP vaccines could be an effective influenza vaccine against homologous and heterologous HPAI viruses.