Comparison of Heterosubtypic Protection in Ferrets and Pigs Induced by a Single-Cycle Influenza Vaccine

Influenza is a major health threat, and a broadly protective influenza vaccinewould be a significant advance. Signal Minus FLU (S-FLU) is a candidate broadly protective influenza vaccinethat is limited to a single cycle of replication, which induces a strong cross-reactive T cell response but a minimal Ab response to hemagglutininafter intranasal or aerosol administration. We tested whether an H3N2 S-FLU can protect pigs and ferrets from heterosubtypic H1N1 influenzachallenge. Aerosol administration of S-FLU to pigs induced lung tissue-resident memory T cellsand reduced lung pathology but not the viral load. In contrast, in ferrets, S-FLU reduced viral replicationand aerosol transmission. Our data show that S-FLU has different protective efficacy in pigs and ferrets, and that in the absence of Ab, lung T cell immunity can reduce disease severity without reducing challenge viral replication.