Likelihood of prior exposure to circulating influenza viruses resulting in cross-protection by CD8+ T cells against emergent H3N2v swine viruses infecting humans.

Outbreaks of influenza in swine can result in potential threats to human public health. A notable occurrence was the emergence of swine-origin H1N1 influenza viruses in 2009. Since then, there have been several documented outbreaks of swine-origin influenza infecting humans in several countries. Sustained events have occurred when H1N1v, H1N2v, and H3N2v swine-origin viruses have infected humans visiting agricultural shows in the US. The predominant H3N2v viruses gained the matrix protein from the A(H1N1)pdm09 viruses, with reported human-to-human transmission raising fears of another pandemic. Current vaccines do not induce secondary cell-mediated immune responses, which may provide cross-protection against novel influenza A subtypes, however, population susceptibility to infection with seasonal influenza is likely to be influenced by cross-reactive CD8+ T-cells directed towards immunogenic peptides derived from viral proteins. This study involved a retrospective review of historical influenza viruses circulating in human populations from 1918 to 2020 to identify evidence of prior circulation of H3N3v immunogenic CD8+ T-cells peptides found in the NP and M1 proteins. We found evidence of prior circulation of H3N2v NP and M1 immunogenic peptides in historical influenza viruses. This provides insight into the population context in which influenza viruses emerge and may help inform immunogenic peptide selection for cytotoxic T-cell lymphocytes (CTL)-inducing influenza vaccines. Next-generation vaccines capable of eliciting CD8+ T-cell-mediated cross-protective immunity may offer a long-term alternative strategy for influenza vaccines.