Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

Abstract

Abstract Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and antigen-specific T cell response in the lung. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8 specific T cell immune response in the lung and cannot prevent infection with PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lung but cannot prevent infection with nH1N1 virus either. Antigen specific T cell immunity is required for sterilizing immunity. We discuss the potential implications of these findings in vaccination strategy for effectual protection comparable to pre-infection.