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Journal of Virology, October 2009, p. 10198-10210, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00926-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Elastase-Dependent Live Attenuated Swine Influenza A Viruses Are Immunogenic and Confer Protection against Swine Influenza A Virus Infection in Pigs{triangledown}

Aleksandar Masic, Jayaum S. Booth, George K. Mutwiri, Lorne A. Babiuk,{dagger} and Yan Zhou*

Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada

Received 8 May 2009/ Accepted 10 July 2009

Influenza A viruses cause significant morbidity in swine, resulting in a substantial economic burden. Swine influenza virus (SIV) infection also poses important human public health concerns. Vaccination is the primary method for the prevention of influenza virus infection. Previously, we generated two elastase-dependent mutant SIVs derived from A/Sw/Saskatchewan/18789/02(H1N1): A/Sw/Sk-R345V (R345V) and A/Sw/Sk-R345A (R345A). These two viruses are highly attenuated in pigs, making them good candidates for a live-virus vaccine. In this study, the immunogenicity and the ability of these candidates to protect against SIV infection were evaluated in pigs. We report that intratracheally administrated R345V and R345A induced antigen-specific humoral and cell-mediated immunity characterized by increased production of immunoglobulin G (IgG) and IgA antibodies in the serum and in bronchoalveolar lavage fluid, high hemagglutination inhibition titers in serum, an enhanced level of lymphocyte proliferation, and higher numbers of gamma interferon-secreting cells at the site of infection. Based on the immunogenicity results, the R345V virus was further tested in a protection trial in which pigs were vaccinated twice with R345V and then challenged with homologous A/Sw/Saskatchewan/18789/02, H1N1 antigenic variant A/Sw/Indiana/1726/88 or heterologous subtypic H3N2 A/Sw/Texas/4199-2/9/98. Our data showed that two vaccinations with R345V provided pigs with complete protection from homologous H1N1 SIV infection and partial protection from heterologous subtypic H3N2 SIV infection. This protection was characterized by significantly reduced macroscopic and microscopic lung lesions, lower virus titers from the respiratory tract, and lower levels of proinflammatory cytokines. Thus, elastase-dependent SIV mutants can be used as live-virus vaccines against swine influenza in pigs.

* Corresponding author. Mailing address: Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK, Canada S7N 5E3. Phone: (306) 966-7716. Fax: (306) 966-7478. E-mail: yan.zhou{at}usask.ca

{triangledown} Published ahead of print on 22 July 2009.

{dagger} Present address: University of Alberta, 3-7 University Hall, Edmonton, Alberta T6G 2J9, Canada.

Journal of Virology, October 2009, p. 10198-10210, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00926-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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