Influenza A viruses with truncated NS1 as modified live virus vaccines: Pilot studies of safety and efficacy in horses

T. M. Chambers, M. Quinlivan, T. Sturgill, A. Cullinane, D. W. Horohov, D. Zamarin, S. Arkins, A. Garcí-Asastre, P. Palese

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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°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-1β 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 live 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.

Original languageEnglish
Pages (from-to)87-92
Number of pages6
JournalEquine Veterinary Journal
Volume41
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Cytokine
  • Equine influenza
  • Horse
  • Intranasal
  • NS-1
  • Reverse genetics
  • Vaccine

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