Induction of CD8 T Cell Heterologous Protection by a Single Dose of Single-cycle Infectious Influenza Virus.
ABSTRACT The effector functions of specific CD8 T cells are crucial in mediating influenza heterologous protection. However, new approaches for influenza vaccines that can trigger effective CD8 T cell responses have not been extensively explored. Here, we report the generation of single cycle infectious influenza virus that lacks a functional HA gene on an X31 genetic background and demonstrate its potential for triggering protective CD8 T cell immunity against heterologous influenza challenge. In vitro, X31-sciIV can infect MDCK cells, but infectious virions are not produced unless HA is trans-complimented. In vivo, intranasal immunization with X31-sciIV does not cause any clinical symptoms in mice but generate influenza specific CD8 T cells in lymphoid (MLN and spleen) and non-lymphoid tissues including lung and BAL as measured by H2-Db NP366 and PA224 tetramer staining. In addition, a significant proportion of X31-sciIV induce, antigen specific respiratory CD8 T cells expressed VLA-1, a marker that is associated with heterologous influenza protection. Further, these influenza specific CD8 T cells produce antiviral cytokines when stimulated with NP366 and PA224 peptides, indicating CD8 T cells triggered by X31-sciIV are functional. When challenged with a lethal dose of heterologous PR8 virus, X31-sciIV primed mice were fully protected from death. However, when CD8 T cells were depleted after priming or before priming, mice could not effectively control virus replication or survive the lethal challenge, indicating X31-sciIV induced memory CD8 T cells mediate the heterologous protection. Thus, our results demonstrate the potential for sciIV as a CD8 T cell inducing vaccine.