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Vaccination using low pathogenic H6N8 can provide protection against highly pathogenic H5N2 but not against highly pathogenic H7N3 in chickens

Session II or VI – Shawn Babiuk

Title of Contribution: Vaccination using low pathogenic H6N8 can provide protection against highly pathogenic H5N2 but not against highly pathogenic H7N3 in chickens

Author(s): Shawn Babiuk1,2, Darwyn Kobasa3,4, Gary Kobinger3,4, Yohannes Berhane1, John Pasisk1, Hana Weingartl1

Affiliation(s):
1National Centre for Foreign Animal Disease, Winnipeg, Manitoba, Canada
2 Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada 3Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
4Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada

Abstract:
The use of vaccination to control avian influenza has been increasing in recent years. Most current vaccination strategies use killed whole virus adjuvanted vaccines that have limited or no protective immunity against heterologous virus challenge, but are effective against homologous challenge. In this study, we explored the possibility of using live low pathogenic avian influenza (LPAI) viruses as vaccines to generate protective immunity against heterologous highly pathogenic avian influenza (HPAI) virus challenge. Twenty chickens were infected by oral, nasal, ocular and cloacal routes with LPAI virus of H6N8 (A/turkey/Ontario/1963) subtype and developed no clinical signs of disease. Virus shedding as determined by matrix real time RT-PCR continued from 3-14 days post infection (dpi). Sera sampled from these chickens at DPI 14 were positive for antibodies using AI nucleoprotein based cELISA. Sera from 14 dpi were also tested by hemagglutination inhibition (HI) assay and were positive for H6 specific antibodies but negative for H5 and H7 hemagglutinin antibodies. After 21 dpi, chickens were divided into 2 groups (10 each) and 10 non vaccinated control chickens were added to each group. Pre-exposed and control chickens in each group were challenged with HPAI viruses of either H5N2 (A/CK/PA/1370/2003/04/11) or H7N3  (A/CK/BC/CN007/26004) subtypes. Vaccinated chickens in the H5N2 group did not exhibit any clinical signs of the disease, whereas control birds developed severe clinical signs and 8 out of 10 birds died. Vaccinated chickens still shed H5N2 virus as demonstrated by H5 based real-time RT-PCR but to a lower extent compared to controls.  Control and vaccinated chickens challenged with H7N3 developed clinical disease and died from the challenge. These results demonstrate that it is possible to protect against a completely heterologous influenza strain using low pathogenic avian influenza. However this protection is not universal. The mechanism for this protection is unknown but likely involves cell mediated immunity at mucosal surfaces. This vaccination approach allows differentiation between vaccinated and infected animals (DIVA) since vaccination with H6N8 does not elicit antibody responses to either H5 or H7 nor N2 or N3.

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