期刊
EQUINE VETERINARY JOURNAL
卷 41, 期 1, 页码 87-92出版社
EQUINE VETERINARY JOURNAL LTD
DOI: 10.2746/042516408X371937
关键词
horse; equine influenza; intranasal; NS-1; cytokine; reverse genetics; vaccine
资金
- NIH [UO1AI070469, HHSN2662000700010C, U54 A1057158-04, 1 UC19 AI062623-023, A1007647]
- USDA/CSREES [KY014028]
- Kentucky Agricultural Experiment Station [08-014-020]
- Department of Agriculture and Food under the National Development Plan
- Irish Research Council for Science. Engineering and Technology
- UK Veterinary Science farm crew
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [T32AI007647, U01AI070469, U54AI057158, U19AI062623] Funding Source: NIH RePORTER
Reasons for performing study: Three previously described NS1 mutant equine influenza viruses encoding carboxy-terminally truncated NS1 proteins are impaired in their ability to inhibit type I IFN production in vitro and are replication attenuated, and thus are candidates for use as a modified live influenza virus vaccine in the horse. Hypothesis: One or more of these mutant viruses is safe when administered to horses, and recipient horses when challenged with wild-type influenza have reduced physiological and virological correlates of disease. Methods: Vaccination and challenge studies were done in horses, with measurement of pyrexia, clinical signs, virus shedding and systemic proinflammatory cytokines. Results: Aerosol or intranasal inoculation of horses with the viruses produced no adverse effects. Seronegative horses inoculated with the NS1-73 and NS1-126 viruses, but not the NS1-99 virus, shed detectable virus and generated significant levels of antibodies. Following challenge with wild-type influenza, horses vaccinated with NS1-126 virus did not develop fever (>38.5 degrees C), had significantly fewer clinical signs of illness and significantly reduced quantities of virus excreted for a shorter duration post challenge compared to unvaccinated controls. Mean levels of proinflammatory cytokines IL-1 beta and IL-6 were significantly higher in control animals, and were positively correlated with peak viral shedding and pyrexia on Day +2 post challenge. Conclusion and clinical relevance: These data suggest that the recombinant NS1 viruses are safe and effective as modified five virus vaccines against equine influenza. This type of reverse genetics-based vaccine can be easily updated by exchanging viral surface antigens to combat the problem of antigenic drift in influenza viruses.
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