tetano
Editor, Senior Moderator
J Virol. 2014 Aug 6. pii: JVI.01847-14. [Epub ahead of print]
Induction of CD8 T Cell Heterologous Protection by a Single Dose of Single-cycle Infectious Influenza Virus.
Guo H1, Baker S2, Mart?nez-Sobrido L2, Topham DJ3.
Author information
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.
IMPORTANCE:
One of the challenges for influenza prevention is its existence of multiple subtypes and variants and the fact that new strains could be emerged yearly. Numerous studies have indicated the effector functions of specific CD8 T cells are crucial in mediating influenza heterologous protection. However, influenza vaccines that can trigger effective CD8 T cell responses for heterologous protection have not been developed. Here, we report the generation of an X31 (H3N2) virus derived single cycle infectious influenza virus, X31-sciIV. One dose immunization with X31-sciIV is capable of inducing functional influenza specific CD8 T cells that can be recruited into respiratory tissues and provide protection for lethal heterologous challenge. Without these cells, protection against lethal challenge was essentially lost. Our data indicate influenza vaccine that primarily relies on CD8 T cells for protection could be developed.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25100831
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25100831
Induction of CD8 T Cell Heterologous Protection by a Single Dose of Single-cycle Infectious Influenza Virus.
Guo H1, Baker S2, Mart?nez-Sobrido L2, Topham DJ3.
Author information
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.
IMPORTANCE:
One of the challenges for influenza prevention is its existence of multiple subtypes and variants and the fact that new strains could be emerged yearly. Numerous studies have indicated the effector functions of specific CD8 T cells are crucial in mediating influenza heterologous protection. However, influenza vaccines that can trigger effective CD8 T cell responses for heterologous protection have not been developed. Here, we report the generation of an X31 (H3N2) virus derived single cycle infectious influenza virus, X31-sciIV. One dose immunization with X31-sciIV is capable of inducing functional influenza specific CD8 T cells that can be recruited into respiratory tissues and provide protection for lethal heterologous challenge. Without these cells, protection against lethal challenge was essentially lost. Our data indicate influenza vaccine that primarily relies on CD8 T cells for protection could be developed.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25100831
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25100831