Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/22/2006
Publication Date: 11/1/2006
Citation: Richt, J.A, Lekcharoensuk, P., Lager, K.M., Vincent, A.L., Loiacono, C.M., Janke, B.H., Wu, W.H., Yoon, K.J., Webby, R.J., Solorzano, A., Garcia-Sastre, A. 2006. Vaccination of pigs against swine influenza viruses by using an NS1-truncated modified live-virus vaccine. Journal of Virology. 80(22):11009-11018. Interpretive Summary: Swine influenza virus (SIV) can naturally infect pigs and be transmitted to humans. Besides SIV, pigs can also be infected by influenza viruses from avian and humans, which can result in the creation of novel influenza viruses. To date, there is no vaccine available inducing cross-protective immunity against different influenza subtypes. Recently we have shown that a genetically altered H3N2 SIV (TX98 NS1delta126) was attenuated in swine, indicating its potential value as modified live virus (MLV) vaccine. Here we describe that the TX98 NS1delta126 completely protected against challenge with the homologous (H3N2) and partially protected against challenge with a heterologous (H1N1) SIV. This indicates that the TX98 NS1delta126 MLV has a great potential as a MLV vaccine.
Technical Abstract: 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 a H3N2 SIV (TX/98) containing a deleted NS1 gene expressing a truncated NS1 protein of 126 amino acids, NS1delta126, was attenuated in swine. In this study, 4-week old pigs were vaccinated with the TX98 NS1delta126 modified live virus (MLV). Ten days after boosting, pigs were challenged with wild type homologous H3N2 or heterosubtypic H1N1 SIVs 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 the non-vaccinated H1N1 control pigs. Remarkably, vaccinated pigs challenged with the H1N1 SIV had significantly lower microscopic lung lesions and reduced virus shedding from the respiratory tract when compared to non-vaccinated, H1N1 challenged pigs. All vaccinated pigs developed significant levels of HI and ELISA titers in serum and mucosal IgA antibodies against H3N2 SIV antigens. Vaccinated pigs were seronegative for NS1, indicating the potential use of the TX98 NS1delta126 MLV as a DIVA (Differentiating Infected from VAccinated individuals) vaccine to differentiate infected from vaccinated animals.