tetano
Editor, Senior Moderator
Nature Immunology | Article
The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus
Rachael Keating,
Tomer Hertz,
Marie Wehenkel,
Tarsha L Harris,
Benjamin A Edwards,
Jennifer L McClaren,
Scott A Brown,
Sherri Surman,
Zachary S Wilson,
Philip Bradley,
Julia Hurwitz,
Hongbo Chi,
Peter C Doherty,
Paul G Thomas
& Maureen A McGargill
Nature Immunology
(2013)
doi:10.1038/ni.2741
Received
11 July 2013
Accepted
13 September 2013
Published online
20 October 2013
Highly pathogenic avian influenza viruses pose a continuing global threat. Current vaccines will not protect against newly evolved pandemic viruses. The creation of 'universal' vaccines has been unsuccessful because the immunological mechanisms that promote heterosubtypic immunity are incompletely defined. We found here that rapamycin, an immunosuppressive drug that inhibits the kinase mTOR, promoted cross-strain protection against lethal infection with influenza virus of various subtypes when administered during immunization with influenza virus subtype H3N2. Rapamycin reduced the formation of germinal centers and inhibited class switching in B cells, which yielded a unique repertoire of antibodies that mediated heterosubtypic protection. Our data established a requirement for the mTORC1 complex in B cell class switching and demonstrated that rapamycin skewed the antibody response away from high-affinity variant epitopes and targeted more conserved elements of hemagglutinin. Our findings have implications for the design of a vaccine against influenza virus.
http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.2741.html
The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus
Rachael Keating,
Tomer Hertz,
Marie Wehenkel,
Tarsha L Harris,
Benjamin A Edwards,
Jennifer L McClaren,
Scott A Brown,
Sherri Surman,
Zachary S Wilson,
Philip Bradley,
Julia Hurwitz,
Hongbo Chi,
Peter C Doherty,
Paul G Thomas
& Maureen A McGargill
Nature Immunology
(2013)
doi:10.1038/ni.2741
Received
11 July 2013
Accepted
13 September 2013
Published online
20 October 2013
Highly pathogenic avian influenza viruses pose a continuing global threat. Current vaccines will not protect against newly evolved pandemic viruses. The creation of 'universal' vaccines has been unsuccessful because the immunological mechanisms that promote heterosubtypic immunity are incompletely defined. We found here that rapamycin, an immunosuppressive drug that inhibits the kinase mTOR, promoted cross-strain protection against lethal infection with influenza virus of various subtypes when administered during immunization with influenza virus subtype H3N2. Rapamycin reduced the formation of germinal centers and inhibited class switching in B cells, which yielded a unique repertoire of antibodies that mediated heterosubtypic protection. Our data established a requirement for the mTORC1 complex in B cell class switching and demonstrated that rapamycin skewed the antibody response away from high-affinity variant epitopes and targeted more conserved elements of hemagglutinin. Our findings have implications for the design of a vaccine against influenza virus.
http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.2741.html