Giuseppe
Emeritus
Letter - Nature advance online publication 17 August 2008 doi:10.1038/nature07231; Received 7 April 2008; Accepted 3 July 2008; Published online 17 August 2008
Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors
Xiaocong Yu 1,6, Tshidi Tsibane 2,6, Patricia A. McGraw 1, Frances S. House 1, Christopher J. Keefer 1, Mark D. Hicar 1, Terrence M. Tumpey 3, Claudia Pappas 2,3, Lucy A. Perrone 3, Osvaldo Martinez 2, James Stevens 3,4, Ian A. Wilson 4, Patricia V. Aguila r2, Eric L. Altschuler 5, Christopher F. Basler 2 & James E. Crowe Jr 1
Departments of Pediatrics and of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
Department of Microbiology, Mount Sinai School of Medicine, New York 10029, USA - Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA - Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA - Department of Physical Medicine and Rehabilitation, University of Medicine & Dentistry of New Jersey, Newark, New Jersey 07103, USA
These authors contributed equally to this work.
Correspondence to: Eric L. Altschuler5Christopher F. Basler2James E.
Crowe Jr1 Correspondence and requests for materials should be addressed to J.E.C. (Email: James.Crowe@vanderbilt.edu), C.F.B. (Email: Chris.Basler@mssm.edu), or E.L.A. (Email: altschel@umdnj.edu).
Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level.
The 1918 H1N1 influenza virus pandemic was the most severe of the modern era1.
Recent work has recovered the gene sequences of this unusual strain2, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes 3, 4.
However, little is known about adaptive immunity to this virus.
We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus.
Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic.
Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA.
We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors.
These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses.
The antibody genes had an unusually high degree of somatic mutation.
The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection.
Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface.
Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure—well into the tenth decade of life.
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http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature07231.html
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Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors
Xiaocong Yu 1,6, Tshidi Tsibane 2,6, Patricia A. McGraw 1, Frances S. House 1, Christopher J. Keefer 1, Mark D. Hicar 1, Terrence M. Tumpey 3, Claudia Pappas 2,3, Lucy A. Perrone 3, Osvaldo Martinez 2, James Stevens 3,4, Ian A. Wilson 4, Patricia V. Aguila r2, Eric L. Altschuler 5, Christopher F. Basler 2 & James E. Crowe Jr 1
Departments of Pediatrics and of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
Department of Microbiology, Mount Sinai School of Medicine, New York 10029, USA - Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA - Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA - Department of Physical Medicine and Rehabilitation, University of Medicine & Dentistry of New Jersey, Newark, New Jersey 07103, USA
These authors contributed equally to this work.
Correspondence to: Eric L. Altschuler5Christopher F. Basler2James E.
Crowe Jr1 Correspondence and requests for materials should be addressed to J.E.C. (Email: James.Crowe@vanderbilt.edu), C.F.B. (Email: Chris.Basler@mssm.edu), or E.L.A. (Email: altschel@umdnj.edu).
Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level.
The 1918 H1N1 influenza virus pandemic was the most severe of the modern era1.
Recent work has recovered the gene sequences of this unusual strain2, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes 3, 4.
However, little is known about adaptive immunity to this virus.
We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus.
Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic.
Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA.
We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors.
These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses.
The antibody genes had an unusually high degree of somatic mutation.
The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection.
Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface.
Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure—well into the tenth decade of life.
-
http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature07231.html
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