Farmer
Senior Moderator
Hope for a new vaccine approach against internal Influenza A proteins that may offer some cross protection against severe infection among subtypes.
Toward a broadly protective influenza vaccine
http://www.jci.org/articles/view/37232
J. Clin. Invest. doi:10.1172/JCI37232.
Peter C. Doherty and Anne Kelso
Commentary:
The current inactivated influenza virus vaccines induce antibodies that protect against closely related virus strains. They do not, however, protect against antibody-escape variants of seasonal influenza A viruses or new pandemic influenza A viruses emerging from non-human reservoirs. Might boosting influenza A virus?specific CD8+ T cell memory diminish the danger posed by these variant viruses? Pre-existing CD8+ T cell?mediated immunity directed at peptides from conserved internal proteins of the influenza A virus does not prevent infection, but it can promote early virus clearance and decrease morbidity in mice. In this issue of the JCI, Lee et al. show that people who have not been exposed to avian influenza A (H5N1) viruses have cross-reactive CD8+ T cell memory to a wide range of H5N1 peptides (see the related article, doi:10.1172/JCI32460). These peptides could be used to add a CD8+ T cell component to current antibody-focused vaccine strategies with a view to reducing the impact of infection with novel influenza A viruses.
Article:
Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals
http://www.jci.org/articles/view/32460
J. Clin. Invest. doi:10.1172/JCI32460.
Laurel Yong-Hwa Lee, Do Lien Anh Ha, Cameron Simmons, et al.
The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4+ and CD8+ memory T cell responses to overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005 (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the United Kingdom and Viet Nam. Memory CD4+ and CD8+ T cells isolated from the majority of participants exhibited human influenza?specific responses and showed cross-recognition of at least one H5N1 internal protein. Participant CD4+ and CD8+ T cells recognized multiple synthesized influenza peptides, including peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of cross-recognition. In addition, cross-reactive CD4+ and CD8+ T cells recognized target cells infected with recombinant vaccinia viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing heterosubtypic T cell?mediated immunity may confer broad protection against avian and human influenza A viruses.
Toward a broadly protective influenza vaccine
http://www.jci.org/articles/view/37232
J. Clin. Invest. doi:10.1172/JCI37232.
Peter C. Doherty and Anne Kelso
Commentary:
The current inactivated influenza virus vaccines induce antibodies that protect against closely related virus strains. They do not, however, protect against antibody-escape variants of seasonal influenza A viruses or new pandemic influenza A viruses emerging from non-human reservoirs. Might boosting influenza A virus?specific CD8+ T cell memory diminish the danger posed by these variant viruses? Pre-existing CD8+ T cell?mediated immunity directed at peptides from conserved internal proteins of the influenza A virus does not prevent infection, but it can promote early virus clearance and decrease morbidity in mice. In this issue of the JCI, Lee et al. show that people who have not been exposed to avian influenza A (H5N1) viruses have cross-reactive CD8+ T cell memory to a wide range of H5N1 peptides (see the related article, doi:10.1172/JCI32460). These peptides could be used to add a CD8+ T cell component to current antibody-focused vaccine strategies with a view to reducing the impact of infection with novel influenza A viruses.
Article:
Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals
http://www.jci.org/articles/view/32460
J. Clin. Invest. doi:10.1172/JCI32460.
Laurel Yong-Hwa Lee, Do Lien Anh Ha, Cameron Simmons, et al.
The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4+ and CD8+ memory T cell responses to overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005 (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the United Kingdom and Viet Nam. Memory CD4+ and CD8+ T cells isolated from the majority of participants exhibited human influenza?specific responses and showed cross-recognition of at least one H5N1 internal protein. Participant CD4+ and CD8+ T cells recognized multiple synthesized influenza peptides, including peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of cross-recognition. In addition, cross-reactive CD4+ and CD8+ T cells recognized target cells infected with recombinant vaccinia viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing heterosubtypic T cell?mediated immunity may confer broad protection against avian and human influenza A viruses.