Influenza A virus infections are a global health threat to humans and are endemic in pigs, contributing to decreased weight gain and suboptimal reproductive performance. Pigs are also a source of new viruses of mixed swine, avian, and human origin, potentially capable of initiating human pandemics. Current inactivated vaccines induce neutralising antibody against the immunising strain but rapid escape occurs through antigenic drift of the surface glycoproteins. However, it is known that prior infection provides a degree of cross-protective immunity mediated by cellular immune mechanisms directed at the more conserved internal viral proteins. Here we review new data that emphasises the importance of local immunity in cross-protection and the role of the recently defined tissue-resident memory T cells, as well as locally-produced, and sometimes cross-reactive, antibody. Optimal induction of local immunity may require aerosol delivery of live vaccines, but it remains unclear how long protective local immunity persists. Nevertheless, a universal vaccine might be extremely useful for disease prevention in the face of a pandemic. As a natural host for influenza A viruses, pigs are both a target for a universal vaccine and an excellent model for developing human influenza vaccines.
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