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

• Published in: Journal of medical virology 2022-02, Vol.94 (2), p.567-574
• Main Authors: Komadina, Naomi, Sullivan, Sheena G., Leder, Karin, McVernon, Jodie
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Animals; B-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Child; Child, Preschool; Cross Protection; Cytotoxicity; Disease Outbreaks; Female; H3N2v; Health risks; Human populations; Humans; immunogenic; Immunogenicity; Infant; Infections; Influenza; Influenza A; Influenza A Virus, H3N2 Subtype - genetics; Influenza A Virus, H3N2 Subtype - immunology; Influenza, Human - immunology; Influenza, Human - virology; Lymphocytes; Lymphocytes T; Male; Matrix protein; Middle Aged; Orthomyxoviridae; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - virology; Outbreaks; Pandemics; Peptides; Proteins; Public health; Retrospective Studies; Swine; Swine flu; T-Lymphocytes, Cytotoxic - immunology; Vaccines; Virology; Viruses; Young Adult
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.27299

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. Highlights Swine origin influenza viruses remain a continuing threat to human health. Current influenza vaccines do not provide protection against novel influenza viruses. CD8+ Tcell immunogenic peptides in the NP and M1 proteins of the H3N2v influenza viruses were investigated for evidence of prior circulation in human influenza viruses. Vaccines based on common CD8+ Tcell immunogenic peptides may be able to mimic cross protection provided by influenza infection.