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doi:10.1016/j.vaccine.2011.10.098 | How to Cite or Link Using DOI
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Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs
Matthew A. Kappesa, b, 1, Matthew R. Sandbulteb, 1, Ratree Plattb, Chong Wangc, Kelly M. Lagera, Jamie N. Henningsona, Alessio Lorussoa, Amy L. Vincenta, Crystal L. Lovinga, James A. Rothb, Marcus E. Kehrli Jr.a, Corresponding Author Contact Information, E-mail The Corresponding Author
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a Virus and Prion Diseases Research Unit, National Animal Disease Center, USDA-ARS, 1920 Dayton Ave, PO Box 70, Ames, IA 50010, USA
b Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA
c Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA, USA
Received 26 July 2011; revised 21 October 2011; Accepted 30 October 2011. Available online 7 November 2011.
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 (NS1Δ126 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 NS1Δ126 TX98 versus wild type TX98. In vivo replication of the truncation mutant was minimal compared to the wild type virus. T-cell responses were greater in magnitude in pigs infected with the wild type virus in in vitro restimulation assays. According to the expression of activation marker CD25, peripheral T cell recall responses in NS1Δ126 TX98 infected pigs were minimal. However, intracellular IFN-γ data indicate that the attenuated virus induced virus-specific CD4+CD8?, CD4+CD8+, CD4?CD8+, and γδ T cells within 28 days. The IFN-γ 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 virus restimulation. Pigs previously infected with wild type TX98 were protected from replication of the H1N1 challenge virus. Vaccination with NS1Δ126 TX98 was associated with significantly lower levels of Th1-associated cytokines in infected lungs but provided partial cross-protection against the H1N1 challenge. These results demonstrate that NS1Δ SIV vaccines can elicit cell-mediated cross-protection against antigenically divergent strains.
Highlights
► Attenuated H3N2 influenza vaccine with truncated NS1 was administered to pigs. ► Vaccine induced broadly reactive mucosal antibodies. ► Vaccine primed T cells which were elevated in peripheral blood after infection. ► Vaccinated animals had reduced shedding of heterosubtypic H1N1 challenge virus.
http://www.sciencedirect.com/science/article/pii/S0264410X11017488
Permissions & Reprints
Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs
Matthew A. Kappesa, b, 1, Matthew R. Sandbulteb, 1, Ratree Plattb, Chong Wangc, Kelly M. Lagera, Jamie N. Henningsona, Alessio Lorussoa, Amy L. Vincenta, Crystal L. Lovinga, James A. Rothb, Marcus E. Kehrli Jr.a, Corresponding Author Contact Information, E-mail The Corresponding Author
Purchase
a Virus and Prion Diseases Research Unit, National Animal Disease Center, USDA-ARS, 1920 Dayton Ave, PO Box 70, Ames, IA 50010, USA
b Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA
c Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA, USA
Received 26 July 2011; revised 21 October 2011; Accepted 30 October 2011. Available online 7 November 2011.
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 (NS1Δ126 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 NS1Δ126 TX98 versus wild type TX98. In vivo replication of the truncation mutant was minimal compared to the wild type virus. T-cell responses were greater in magnitude in pigs infected with the wild type virus in in vitro restimulation assays. According to the expression of activation marker CD25, peripheral T cell recall responses in NS1Δ126 TX98 infected pigs were minimal. However, intracellular IFN-γ data indicate that the attenuated virus induced virus-specific CD4+CD8?, CD4+CD8+, CD4?CD8+, and γδ T cells within 28 days. The IFN-γ 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 virus restimulation. Pigs previously infected with wild type TX98 were protected from replication of the H1N1 challenge virus. Vaccination with NS1Δ126 TX98 was associated with significantly lower levels of Th1-associated cytokines in infected lungs but provided partial cross-protection against the H1N1 challenge. These results demonstrate that NS1Δ SIV vaccines can elicit cell-mediated cross-protection against antigenically divergent strains.
Highlights
► Attenuated H3N2 influenza vaccine with truncated NS1 was administered to pigs. ► Vaccine induced broadly reactive mucosal antibodies. ► Vaccine primed T cells which were elevated in peripheral blood after infection. ► Vaccinated animals had reduced shedding of heterosubtypic H1N1 challenge virus.
http://www.sciencedirect.com/science/article/pii/S0264410X11017488