Classical swine H1N1 influenza viruses confer cross protection from swine-origin 2009 pandemic H1N1 influenza virus infection in mice and ferrets

In recent years, influenza viruses with pandemic potential have been a major concern worldwide. One unresolved issue is how infection or vaccination with seasonal influenza virus strains influences the ability to mount a protective immune response to novel pandemic strains. In this study, we developed a mouse model of primary and secondary influenza infection by using a widely circulating seasonal H1N1 virus and the pandemic strain of H1N1 that emerged in Mexico in 2009, and we evaluated several key issues. First, using overlapping peptide libraries encompassing the entire translated sequences of 5 major influenza virus proteins, we assessed the specificity of CD4 T cell reactivity toward epitopes conserved among H1N1 viruses or unique to the seasonal or pandemic strain by enzyme-linked immunospot (ELISpot) assays. Our data show that CD4 T cells reactive to both virus-specific and genetically conserved epitopes are elicited, allowing separate tracking of these responses. Populations of cross-reactive CD4 T cells generated from seasonal influenza infection were found to expand earlier after secondary infection with the pandemic H1N1 virus than CD4 T cell populations specific for new epitopes. Coincident with this rapid CD4 T cell response was a potentiated neutralizing-antibody response to the pandemic strain and protection from the pathological effects of infection with the pandemic virus. This protection was not dependent on CD8 T cells. Together, our results indicate that exposure to seasonal vaccines and infection elicits CD4 T cells that promote the ability of the mammalian host to mount a protective immune response to pandemic strains of influenza virus.

Section: Resultssupporting

confidence: 93%

supporting

confidence: 58%

Infection with Seasonal Influenza Virus Elicits CD4 T Cells Specific for Genetically Conserved Epitopes That Can Be Rapidly Mobilized for Protective Immunity to Pandemic H1N1 Influenza Virus

Alam

Sant

2011

“…In addition, nasal symptoms such as sneezing or nasal discharge were not observed. This was consistent with the results from previous studies using ferrets of a similar age (45).…”

Section: Effectsupporting

confidence: 93%

“…Ferrets primed with the homologous CA/09 or NJ/76 virus served as a positive control, while the negative control was an influenza B virus (B/Mal) that would not cross-protect against influenza A virus infection (20). NJ/76, which caused limited infections in humans and never circulated among the general population, is a genetically and antigenically related swine origin H1N1 virus previously shown to protect against CA/09 virus infection (31,45).…”

Section: Virusesmentioning

confidence: 99%

Effect of Priming with H1N1 Influenza Viruses of Variable Antigenic Distances on Challenge with 2009 Pandemic H1N1 Virus

O’Donnell

Wright

Vogel

et al. 2012

Self Cite

“…There is circumstantial evidence from human studies and animal models that T cells recognizing conserved epitopes can mediate heterotypic immunity against divergent influenza virus strains in the absence of crossreactive NAbs (15)(16)(17)(18)(19)(20)(21)(22), though this concept has so far been tested directly only in mice (21). Accordingly, a number of studies have suggested that infection with seasonal influenza virus provides a level of protection against the swine-origin pandemic 2009 influenza virus (H1N1pdm) in the absence of NAbs, an effect which may be mediated by cross-reactive T cell responses (17,(23)(24)(25)(26)(27)(28). However, the degree to which T cells can mediate effective, longlived heterotypic immunity to influenza in humans remains unclear.…”

mentioning

confidence: 99%

Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques

Jegaskanda

Weinfurter

Friedrich

et al. 2013

171

169

Furthermore, we found that influenza virus-specific ADCC was present in bronchoalveolar lavage fluid and was able to activate lung NK cells. We concluded that infection with a seasonal influenza virus can induce antibodies that mediate ADCC capable of recognizing divergent influenza virus strains. Cross-reactive ADCC may provide a mechanism for reducing the severity of divergent influenza virus infections.