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

J Immunol. 2018 Jun 15;200(12):4068-4077. doi: 10.4049/jimmunol.1800142. Epub 2018 Apr 27.

Abstract

Influenza is a major health threat, and a broadly protective influenza vaccine would be a significant advance. Signal Minus FLU (S-FLU) is a candidate broadly protective influenza vaccine that is limited to a single cycle of replication, which induces a strong cross-reactive T cell response but a minimal Ab response to hemagglutinin after intranasal or aerosol administration. We tested whether an H3N2 S-FLU can protect pigs and ferrets from heterosubtypic H1N1 influenza challenge. Aerosol administration of S-FLU to pigs induced lung tissue-resident memory T cells and reduced lung pathology but not the viral load. In contrast, in ferrets, S-FLU reduced viral replication and 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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / immunology
  • Cross Reactions / immunology
  • Ferrets
  • Hemagglutinins / immunology
  • Humans
  • Immunity / immunology
  • Immunologic Memory / immunology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza Vaccines / immunology*
  • Orthomyxoviridae Infections / immunology*
  • Swine
  • T-Lymphocytes / immunology
  • Vaccination / methods
  • Virus Replication / immunology

Substances

  • Antibodies, Viral
  • Hemagglutinins
  • Influenza Vaccines