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Sci Transl Med 14 August 2013:
Vol. 5, Issue 198, p. 198ra107
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3006637
Research Article
INFLUENZA
Neutralizing Antibodies Against Previously Encountered Influenza Virus Strains Increase over Time: A Longitudinal Analysis
Matthew S. Miller1,
Thomas J. Gardner1,
Florian Krammer1,
Lauren C. Aguado1,
Domenico Tortorella1,
Christopher F. Basler1 and
Peter Palese1,2,*
+ Author Affiliations
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
2Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
↵*Corresponding author. E-mail: peter.palese@mssm.edu
Abstract
Antigenic diversity shapes immunity in distinct and unexpected ways. This is particularly true of the humoral response generated against influenza A viruses. Although it is known that immunological memory developed against previously encountered influenza A virus strains affects the outcome of subsequent infections, exactly how sequential exposures to antigenically variant viruses shape the humoral immune response in humans remains poorly understood. To address this important question, we performed a longitudinal analysis of antibody titers against various pandemic and seasonal strains of influenza virus spanning a 20-year period (1987 to 2008) with samples from 40 individuals (birth dates, 1917 to 1952) obtained from the Framingham Heart Study. Longitudinal increases in neutralizing antibody titers were observed against previously encountered pandemic H2N2, H3N2, and H1N1 influenza A virus strains. Antibody titers against seasonal strains encountered later in life also increased longitudinally at a rate similar to that against their pandemic predecessors. Titers of cross-reactive antibodies specific to the hemagglutinin stalk domain were also investigated because they are influenced by exposure to antigenically diverse influenza A viruses. These titers rose modestly over time, even in the absence of major antigenic shifts. No sustained increase in neutralizing antibody titers against an antigenically more stable virus (human cytomegalovirus) was observed. The results herein describe a role for antigenic variation in shaping the humoral immune compartment and provide a rational basis for the hierarchical nature of antibody titers against influenza A viruses in humans.
Copyright ? 2013, American Association for the Advancement of Science
Vol. 5, Issue 198, p. 198ra107
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3006637
Research Article
INFLUENZA
Neutralizing Antibodies Against Previously Encountered Influenza Virus Strains Increase over Time: A Longitudinal Analysis
Matthew S. Miller1,
Thomas J. Gardner1,
Florian Krammer1,
Lauren C. Aguado1,
Domenico Tortorella1,
Christopher F. Basler1 and
Peter Palese1,2,*
+ Author Affiliations
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
2Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
↵*Corresponding author. E-mail: peter.palese@mssm.edu
Abstract
Antigenic diversity shapes immunity in distinct and unexpected ways. This is particularly true of the humoral response generated against influenza A viruses. Although it is known that immunological memory developed against previously encountered influenza A virus strains affects the outcome of subsequent infections, exactly how sequential exposures to antigenically variant viruses shape the humoral immune response in humans remains poorly understood. To address this important question, we performed a longitudinal analysis of antibody titers against various pandemic and seasonal strains of influenza virus spanning a 20-year period (1987 to 2008) with samples from 40 individuals (birth dates, 1917 to 1952) obtained from the Framingham Heart Study. Longitudinal increases in neutralizing antibody titers were observed against previously encountered pandemic H2N2, H3N2, and H1N1 influenza A virus strains. Antibody titers against seasonal strains encountered later in life also increased longitudinally at a rate similar to that against their pandemic predecessors. Titers of cross-reactive antibodies specific to the hemagglutinin stalk domain were also investigated because they are influenced by exposure to antigenically diverse influenza A viruses. These titers rose modestly over time, even in the absence of major antigenic shifts. No sustained increase in neutralizing antibody titers against an antigenically more stable virus (human cytomegalovirus) was observed. The results herein describe a role for antigenic variation in shaping the humoral immune compartment and provide a rational basis for the hierarchical nature of antibody titers against influenza A viruses in humans.
Copyright ? 2013, American Association for the Advancement of Science
