T Cell-Mediated Protection against Lethal 2009 Pandemic H1N1 Influenza Virus Infection in a Mouse Model

Guo, Hailong; Santiago, Felix W.; Lambert, Kris N.; Takimoto, Toru; Topham, David J.

doi:10.1128/jvi.01812-10

Cited by 98 publications

(130 citation statements)

References 39 publications

Supporting

Mentioning

121

Contrasting

Order By: Relevance

“…Therefore, a single infection with, and clearance of, a seasonal H1N1 virus can provide immunological protection from a lethal dose of the distantly related pandemic strain. This conclusion is in agreement with recently published work using different H1N1 virus strains in ferrets (39) and C57BL/6 mice (27,39) and with recent studies showing the ability of the commercial FluMist vaccine to protect C3H and C57BL/6 mice from future infection with the pandemic H1N1 virus (62).…”

Section: Resultssupporting

confidence: 82%

“…Influenza virus A/California/04/2009 E3 (referred to below as A/California; generously provided by David Topham at the University of Rochester) is known to contain alterations in the HA gene resulting in three amino acid differences from the original strain isolated from humans (27).…”

Section: Influenza Virusmentioning

confidence: 99%

“…Although recent experimental work with ferrets and mice indicates that preexposure to a seasonal H1N1 virus can provide protective immunity to a later challenge with the 2009 H1N1 virus (27,62), few studies have directly examined the scope or specificity of CD4 T cells that are cross-reactive for seasonal and pandemic H1N1 viruses. Understanding the specificity of CD4 T cells is essential for several reasons.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

J Virol

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 82%

Section: Influenza Virusmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

J Virol

View full text Add to dashboard Cite

show abstract

“…The correlation of virus-specific CD8 + T-cells with immunity to other subtypes has been demonstrated previously by using various combinations of subtypes (Grebe et al, 2008;Kreijtz et al, 2007Kreijtz et al, , 2009O'Neill et al, 2000;Seo & Webster, 2001) and in various animal species; including immunity to 2009 pH1N1 viruses induced by infection with sH3N2 virus (Guo et al, 2011;Skountzou et al, 2010). To demonstrate that virus-specific T-cell responses not only correlated with protection but were also directly responsible for heterosubtypic immunity, we performed adoptive transfer experiments.…”

Section: T-cells Provide Protection Against Infection With Ph1n1mentioning

confidence: 99%

Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells

Hillaire

Trierum

Kreijtz

et al. 2011

Journal of General Virology

112

View full text Add to dashboard Cite

Influenza A (H1N1) viruses of swine origin were introduced into the human population in 2009 and caused a pandemic. The disease burden in the elderly was relatively low, which was attributed to the presence of cross-reacting serum antibodies in this age group, which were raised against seasonal influenza A (H1N1) viruses that circulated before 1957. It has also been described how infection with heterosubtypic influenza viruses can induce some degree of protection against infection by a novel strain of influenza virus. Here, we assess the extent of protective immunity against infection with the 2009 influenza A (H1N1) pandemic influenza virus that is afforded by infection with a seasonal influenza A (H3N2) virus in mice. Mice that experienced a primary A (H3N2) influenza virus infection displayed reduced weight loss after challenge infection and cleared the 2009 influenza A (H1N1) virus infection more rapidly. To elucidate the correlates of protection of this heterosubtypic immunity to pandemic H1N1 virus infection, adoptive transfer experiments were carried out by using selected post-infection lymphocyte populations. Virus-specific CD8+ T-cells in concert with CD4+ T-cells were responsible for the observed protection. These findings may not only provide an explanation for epidemiological differences in the incidence of severe pandemic H1N1 infections, they also indicate that the induction of cross-reactive virus-specific CD8+ and CD4+ T-cell responses may be a suitable approach for the development of universal influenza vaccines.

show abstract

“…In contrast, heterosubtypic immunity is defined as immunity to an influenza subtype (i.e., heterologous influenza A virus that has a major change in the surface proteins [antigenic shift]). There is strong evidence in animal models that influenza-specific cross-reactive memory T cells are responsible for inducing heterosubtypic immunity (5)(6)(7). However, in humans, the role of cross-reactive memory T cells in protecting against influenza is not well elucidated.…”

mentioning

confidence: 99%

Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection

Pichyangkul

Yongvanitchit

Limsalakpetch

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Studies of influenza-specific immune responses in humans have largely assessed systemic responses involving serum Ab and peripheral blood T cell responses. However, recent evidence indicates that tissue-resident memory T (TRM) cells play an important role in local murine intrapulmonary immunity. Rhesus monkeys were pulmonary exposed to 2009 pandemic H1N1 virus at days 0 and 28 and immune responses in different tissue compartments were measured. All animals were asymptomatic postinfection. Although only minimal memory immune responses were detected in peripheral blood, a high frequency of influenza nucleoprotein–specific memory T cells was detected in the lung at the “contraction phase,” 49–58 d after second virus inoculation. A substantial proportion of lung nucleoprotein-specific memory CD8+ T cells expressed CD103 and CD69, phenotypic markers of TRM cells. Lung CD103+ and CD103- memory CD8+ T cells expressed similar levels of IFN-γ and IL-2. Unlike memory T cells, spontaneous Ab secreting cells and memory B cells specific to influenza hemagglutinin were primarily observed in the mediastinal lymph nodes. Little difference in systemic and local immune responses against influenza was observed between young adult (6–8 y) and old animals (18–28 y). Using a nonhuman primate model, we revealed substantial induction of local T and B cell responses following 2009 pandemic H1N1 infection. Our study identified a subset of influenza-specific lung memory T cells characterized as TRM cells in rhesus monkeys. The rhesus monkey model may be useful to explore the role of TRM cells in local tissue protective immunity after rechallenge and vaccination.

show abstract

T Cell-Mediated Protection against Lethal 2009 Pandemic H1N1 Influenza Virus Infection in a Mouse Model

Cited by 98 publications

References 39 publications

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

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

Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells

Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection

Contact Info

Product

Resources

About