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Journal of Virology, November 2006, p. 11009-11018, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00787-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Vaccination of Pigs against Swine Influenza Viruses by Using an NS1-Truncated Modified Live-Virus Vaccine{triangledown}

Jürgen A. Richt,1,{ddagger}* Porntippa Lekcharoensuk,2,{dagger},{ddagger} Kelly M. Lager,1 Amy L. Vincent,1 Christina M. Loiacono,2 Bruce H. Janke,2 Wai-Hong Wu,2 Kyoung-Jin Yoon,2 Richard J. Webby,3 Alicia Solórzano,4 and Adolfo García-Sastre4

Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa 50010,1 Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011,2 Division of Virology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,3 Department of Microbiology, Mount Sinai School of Medicine, New York, New York 100294

Received 18 April 2006/ Accepted 22 August 2006

Swine influenza viruses (SIV) naturally infect pigs and can be transmitted to humans. In the pig, genetic reassortment to create novel influenza subtypes by mixing avian, human, and swine influenza viruses is possible. An SIV vaccine inducing cross-protective immunity between different subtypes and strains circulating in pigs is highly desirable. Previously, we have shown that an H3N2 SIV (A/swine/Texas/4199-2/98 [TX98]) containing a deleted NS1 gene expressing a truncated NS1 protein of 126 amino acids, NS1{blacktriangleup}126, was attenuated in swine. In this study, 4-week-old pigs were vaccinated with the TX98 NS1{blacktriangleup}126 modified live virus (MLV). Ten days after boosting, pigs were challenged with wild-type homologous H3N2 or heterosubtypic H1N1 SIV and sacrificed 5 days later. The MLV was highly attenuated and completely protected against challenge with the homologous virus. Vaccinated pigs challenged with the heterosubtypic H1N1 virus demonstrated macroscopic lung lesions similar to those of the unvaccinated H1N1 control pigs. Remarkably, vaccinated pigs challenged with the H1N1 SIV had significantly lower microscopic lung lesions and less virus shedding from the respiratory tract than did unvaccinated, H1N1-challenged pigs. All vaccinated pigs developed significant levels of hemagglutination inhibition and enzyme-linked immunosorbent assay titers in serum and mucosal immunoglobulin A antibodies against H3N2 SIV antigens. Vaccinated pigs were seronegative for NS1, indicating the potential use of the TX98 NS1{blacktriangleup}126 MLV as a vaccine to differentiate infected from vaccinated animals.

* Corresponding author. Mailing address: Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 2300 Dayton Ave. B-15, Ames, IA 50010. Phone: (515) 663-7366. Fax: (515) 663-7458. E-mail: jricht{at}nadc.ars.usda.gov.

{triangledown} Published ahead of print on 30 August 2006.

{ddagger} Both authors contributed equally to the work.

{dagger} Present address: Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand.

Journal of Virology, November 2006, p. 11009-11018, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00787-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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