Heterosubtypic T‐cell responses against avian influenza H5 haemagglutinin are frequently detected in individuals vaccinated against or previously infected with human subtypes of influenza

Abstract

Background Cellula r immune responses play a critical role in providing help for the production of neutralizing antibodies to influenza virus, as well as producing anti‐viral cytokines and killing infected cells in the lung. Heterosubtypic T‐cell responses between different subtypes of influenza have been shown to exist in humans and to provide protection against morbidity and mortality associated with H5N1 infection in animal challenge models. Therefore, existing T‐cell responses induced by natural infection or vaccination in humans may provide some degree of protection from infection with H5N1 strains, or may attenuate the severity of disease. Objectives To investigate heterosubtypic T‐cell responses to avian influenza in humans. Methods T‐cell responses to an overlapping set of H5 HA peptides and inactivated viruses (H1N1, H3N2 and H5N1) were assessed using IFN‐γ and IL‐2 enzyme‐linked immunospot (ELISpot) assays in a cohort of adults either vaccinated against seasonal influenza in the last 3 years (n = 20) or previously infected (n = 40). Results T‐cell responses to all three subtypes of virus were found in both infected and vaccinated individuals by IFN‐γ and IL‐2 ELISpot assays. Approximately half of the participants from each group had a positive T‐cell response to the H5 HA peptides in the IFN‐γ or IL‐2 ELISpot assay. Conclusions Heterosubtypic T‐cell responses to H5 HA occur quite frequently in vaccinated and infected individuals. Further investigation of these responses and what role they may play upon challenge or vaccination against H5N1 may assist in vaccine design for avian influenza.

Avian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity

“…Early reports indicated that memory CD8 + (and CD4 + ) T cells from healthy individuals with no documented history of prior exposure to avian influenza could recognize epitopes from avian-derived viruses, including 1997 Hong Kong H5N1 ( 119 ). The cross-reactive nature of influenza-specific CD8 + T cells was further demonstrated by several groups ( 120 – 122 ), which reported heterosubtypic memory T cell responses against avian H5N1 in healthy individuals without prior exposure to AIV. This heterosubtypic immunity was proposed to provide at least some level of protection toward the new emerging, possibly pandemic, influenza AIV strains.…”

Coupling sensitive in vitro and in silico techniques to assess cross-reactive CD4+ T cells against the swine-origin H1N1 influenza virus

“…Our inability to detect individual peptide-specific responses by ELISPOT is not surprising given other researchers have experienced similar difficulties using this technique to evaluate direct ex vivo T cell responses in humans [43, 44]. In fact, past studies aimed at evaluating individual peptide-specific T cell responses from humans have resorted to long-term in vitro stimulation periods (up to 10 day) to trigger the proliferation/accumulation of the specific lymphocytes to a number where they could be detected by ELISPOT assay [28].…”

Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice

“…In contrast, recovery from natural infection or from inoculation with live influenza viruses induces cross protective immunity against different subtypes of influenza viruses (i.e., heterosubtypic immunity) that is thought to be primarily mediated by T cells that recognize conserved epitopes of internal proteins, including nucleoprotein (NP) and matrix (M) [35–37]. The importance of heterosubtypic immunity in human populations is debated, but evidence suggests that cross protective immune responses, including neutralizing antibodies and T cells, exist and may be important for protection against new circulating strains of influenza A viruses, such as pandemic 2009 H1N1 [38–40] and avian H5N1 influenza virus [41, 42]. In rodent models, primary infection with a sublethal dose of influenza A virus induces cross-protective immunity against lethal infection with a heterosubtypic virus strain [43–48].…”