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

Abstract

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.

Infection of the Upper Respiratory Tract with Seasonal Influenza A(H3N2) Virus Induces Protective Immunity in Ferrets against Infection with A(H1N1)pdm09 Virus after Intranasal, but Not Intratracheal, Inoculation

“…Similar results were also obtained in a mouse model using intranasal inoculation for priming and administration of challenge virus (15,21), but it should be emphasized that the mode of action and the protective mechanisms in mice may be fundamentally different from those in ferrets.…”

“…A prior infection with a seasonal human influenza A virus of the H3N2 subtype also afforded a certain degree of protection against infection with A(H1N1)pdm09 virus (17,21,22). Infection with an influenza A virus does not induce sterilizing immu-nity but can mitigate the clinical signs caused by a subsequent infection with a (pandemic) virus of another subtype.…”

“…Indeed, adoptive transfer of T cells induced by influenza A(H3N2) virus infection afforded recipient mice protection against A(H1N1)pdm09 virus (21). In contrast to antibodies against the stem region of the hemagglutinin, virus-specific CD4 ϩ and CD8 ϩ T cells directed against conserved inner proteins are able to afford protection against all subtypes of influenza A virus, regardless of the hemagglutinin group.…”

Intranasal Adenovirus-Vectored Vaccine for Induction of Long-Lasting Humoral Immunity-Mediated Broad Protection against Influenza in Mice

“…Although rAd vectors are effective at induction of T cell responses that play a role in HSI (55,56), our results indicate that Abs induced by the rAd-vectored vaccines readily mediate HSI since adoptive transfer of antisera containing specific Abs conferred protection against infection with another subtype. This is supported by further findings that adoptive transfer of an Ig-containing fraction, but not of a non-Ig-containing fraction of antisera provided protection (Fig.…”

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“…As was shown in animal models, the cell immune response might have a protective role in case of homological and heterological infections [29][30][31][32][33][34][35]. The results of the adaptive transfer of T-cells from the primed mice to the naive recipients prove the protective function of the CD4 + and CD8 + cells [36]. The protective function of the preexisting virus specific T-cells CD4 + and CD8 + was also shown in humans in case of experimental [37,38] and natural infection by the pandemic virus H1N1 of 2009 [39].…”