|Kehrli jr, Marcus|
Submitted to: Vaccine
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/30/2011
Publication Date: 1/5/2012
Citation: Kappes, M.A., Sandbulte, M.R., Platt, R., Wang, C., Lager, K.M., Henningson, J.N., Lorusso, A., Vincent, A.L., Loving, C.L., Roth, J.A., Kehrli Jr, M.E. 2012. Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs. Vaccine. 30(2):280-288. Interpretive Summary: Influenza A virus causes a respiratory disease in swine similar to that in humans. Use of killed influenza virus vaccines in swine has increased over the past ten years in an effort to prevent disease and transmission of the virus. However, killed vaccines only work well when pigs are exposed to influenza viruses represented in the vaccine and vaccine efficacy is reduced when pigs are infected with new strains. This is an issue because there is a diversity of influenza virus subtypes circulating in pigs (H3N2 and H1N1) and within these subtypes there is additional diversity. In this report, we report evidence that a modified live H3N2 swine influenza vaccine administered to pigs provided some cross-protective immunity when followed by infection with an H1N1 swine influenza virus and that cell mediated immunity which is mainly induced by live vaccine viruses may be an important component to this cross protection. Future vaccines that stimulate improved immune responses across differing influenza viruses will be important to prevent infection and clinical disease and reduce the burden of this economically important disease. Since influenza viruses from swine may infect people and visa versa, controlling influenza in the swine population has important implications to human health.
Technical Abstract: The diversity of contemporary swine influenza virus (SIV) strains impedes effective immunization of swine herds. Mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad cross-protection. Reverse genetics-derived H3N2 SIV virus with truncated NS1 (NS1delta126 TX98) is attenuated and immunogenic when delivered intranasally in young pigs. We analyzed T-cell priming and cross-protective efficacy in weanling piglets after intranasal inoculation with NS1delta126 TX98 versus wild type TX98. In vivo replication of the truncation mutant was several logs lower than the wild type virus. In vitro restimulation assays showed that T-cell responses were greater in pigs infected with the wild type virus. According to the expression of activation marker CD25, peripheral T cell recall responses in NS1delta126 TX98 infected pigs were minimal. However, intracellular IFN-gamma data indicate that the attenuated virus induced virus-specific CD4+CD8–, CD4+CD8+, CD4–CD8+, and gamma-delta T cells within 28 days. The IFN-gamma response appeared to contract, as responses were reduced at later time points prior to challenge. CD4+CD8+ cells isolated 5 days after heterosubtypic H1N1 challenge (day 70 overall) showed an elevated CD25 response to viral restimulation. Replication of the H1N1 challenge virus was largely blocked in pigs previously infected with wild type TX98. Vaccination with NS1delta126 TX98 was also partially cross-protective, despite being associated with significantly lower levels of Th1-associated cytokines in infected lungs. These results support the concept that NS1deltaSIV vaccines can elicit cell-mediated cross-protection against antigenically divergent strains.