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.