Cross-reactive influenza H1N1 T cell epitopes identified by immunoinformatic methods stimulate CD4+ T cell responses (P4303)

Abstract

Immune responses to cross-conserved T cell epitopes in novel H1N1 influenza might explain reports of diminished influenza-like illnesses and confirmed infection among older adults, in the absence of cross-reactive humoral immunity, during the 2009 pandemic. We set out to identify and characterize cross-conserved H1N1 T cell epitopes to develop a universal H1N1 influenza vaccine. An immunoinformatic analysis was conducted using all available pandemic and pre-pandemic HA-H1 and NA-N1 sequences dating back to 1980. From 5,738 HA-H1 and 5,396 NA-N1 sequences, 13 HA and 4 NA immunogenic consensus sequences (ICS) were selected that each cover >84% of pre-pandemic and pandemic H1N1 influenza strains, bear EpiMatrix scores ≥95th percentile and cover ≥4 HLA Class II archetypal alleles. HLA binding assays for 6 Class II archetypal alleles showed that immunoinformatic predictions were 78% accurate. Individual ICS peptides were immunoreactive in cultured human IFNy ELISpot assays after antigen-specific in vitro expansion. Intracellular cytokine staining showed the magnitude of IL-2, IFNy and/or TNFa expressing CD4+ T cells was boosted by 2011 seasonal trivalent influenza immunization for vaccine-matched and ICS HA peptide pools. Immunoinformatic methods identify cross-reactive influenza H1N1-specific CD4+ T cell epitopes. This approach can be applied to other influenza subtypes to develop a universal influenza vaccine that will protect against antigenically novel influenza viruses.