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Equine veterinary journal2009; 41(1); 87-92; doi: 10.2746/042516408x371937

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

Abstract: 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. Objective: 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-1beta and IL-6 were significantly higher in control animals, and were positively correlated with peak viral shedding and pyrexia on Day +2 post challenge. Conclusions: 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.
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Publication Date: 2009-03-24 PubMed ID: 19301588PubMed Central: PMC2878972DOI: 10.2746/042516408x371937Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study explores the safety and effectiveness of using NS1 mutant equine influenza viruses with truncated NS1 proteins as a live influenza virus vaccine for horses. The results suggest that these viruses are safe for use and can help to reduce the physiological and virological signs of disease.

Objective

The main objective of this study was to investigate the safety and efficacy of NS1 mutant equine influenza viruses as a modified live virus vaccine for horses. The hypothesis was that these NS1 mutant viruses would not trigger any adverse effects in the horses, and that the horses would demonstrate reduced signs of illness and decreased virus shedding when challenged with wild-type influenza.

Methods

  • The study was undertaken using vaccination and challenge protocols in horses.
  • The team recorded observations pertaining to fever, signs of illness, virus shedding, and systemic proinflammatory cytokines.
  • The horses were initially exposed to the NS1-73, NS1-99, and NS1-126 viruses and any resulting virus shedding and the generation of antibodies were observed and assessed.
  • Following this, the horses were challenged with wild-type influenza to evaluate how the NS1 mutant viruses would respond.

Results

  • The application of the NS1 mutant viruses through aerosol or intranasal methods did not lead to any adverse effects in the horses.
  • It was seen that horses exposed to the NS1-73 and NS1-126 viruses, but not the NS1-99, shed detectable virus and produced significant levels of antibodies.
  • Horses vaccinated with the NS1-126 virus did not develop a fever, showed significantly fewer signs of illness, and had drastically reduced quantities of virus over a shorter period post wild-type influenza challenge as compared to the control or unvaccinated animals.
  • Proinflammatory cytokines IL-1beta and IL-6 were found to be significantly higher in the control group, and were linked with peak viral shedding and fever development.

Conclusions

The conclusions drawn from this study were that the NS1 mutant equine influenza viruses are safe and potent as a live virus vaccine against equine influenza. The recombinant NS1 viruses also present a potential solution to the issue of antigenic drift in influenza viruses, as this method-based vaccine can be easily updated by changing the viral surface antigens.

Cite This Article

APA
Chambers TM, Quinlivan M, Sturgill T, Cullinane A, Horohov DW, Zamarin D, Arkins S, García-Sastre A, Palese P. (2009). Influenza A viruses with truncated NS1 as modified live virus vaccines: pilot studies of safety and efficacy in horses. Equine Vet J, 41(1), 87-92. https://doi.org/10.2746/042516408x371937

Publication

Equine veterinary journal
ISSN: 0425-1644
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 41
Issue: 1
Pages: 87-92

Researcher Affiliations

Chambers, T M
  • Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Quinlivan, M
    Sturgill, T
      Cullinane, A
        Horohov, D W
          Zamarin, D
            Arkins, S
              García-Sastre, A
                Palese, P

                  MeSH Terms

                  • Administration, Intranasal
                  • Animals
                  • Antibodies, Viral / blood
                  • Cytokines / biosynthesis
                  • Horse Diseases / immunology
                  • Horse Diseases / prevention & control
                  • Horse Diseases / virology
                  • Horses
                  • Influenza A Virus, H3N8 Subtype / immunology
                  • Influenza Vaccines / adverse effects
                  • Influenza Vaccines / genetics
                  • Influenza Vaccines / immunology
                  • Nebulizers and Vaporizers / veterinary
                  • Orthomyxoviridae Infections / immunology
                  • Orthomyxoviridae Infections / prevention & control
                  • Orthomyxoviridae Infections / veterinary
                  • Orthomyxoviridae Infections / virology
                  • Pilot Projects
                  • Recombination, Genetic
                  • Safety
                  • Time Factors
                  • Treatment Outcome
                  • Vaccination / veterinary
                  • Vaccines, Attenuated / adverse effects
                  • Vaccines, Attenuated / immunology
                  • Viral Nonstructural Proteins / genetics
                  • Viral Nonstructural Proteins / immunology
                  • Virus Shedding

                  Grant Funding

                  • T32 AI007647 / NIAID NIH HHS
                  • U01 AI070469 / NIAID NIH HHS
                  • U19 AI062623-050003 / NIAID NIH HHS
                  • AI007647 / NIAID NIH HHS
                  • U01 AI070469-03 / NIAID NIH HHS
                  • U01AI070469 / NIAID NIH HHS
                  • T32 AI007647-10 / NIAID NIH HHS
                  • U54 AI057158 / NIAID NIH HHS
                  • HHSN2662000700010C / AHRQ HHS
                  • U19 AI062623 / NIAID NIH HHS
                  • U54 AI057158-04 / NIAID NIH HHS
                  • HHNSN266200700010C / PHS HHS
                  • HHSN266200700010C / NIAID NIH HHS
                  • U54 AI057158-05S10003 / NIAID NIH HHS

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