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Cell Host Microbe. 2019 Mar 13;25(3):357-366.e6. doi: 10.1016/j.chom.2019.01.002. Epub 2019 Feb 19.

Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals.

Author information

1
Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: carolehenry@uchicago.edu.
2
Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637, USA.
3
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Department of Ecology and Evolution, The University of Chicago, Chicago, IL 60637, USA.
5
Emory Vaccine Center, Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30317, USA.
6
Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30317, USA.
7
Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
8
Center for Vaccine Biology & Immunology, Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
9
Division of Infectious Disease, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
10
The Wistar Institute Vaccine and Immunotherapy Center, Philadelphia, PA 19104, USA.
11
Division of Geriatrics, Duke University Medical Center and GRECC, Durham VA Medical Center, Durham, NC 27710, USA.
12
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
13
Departments of Medicine and Immunology and Microbiology, Stanford University School of Medicine, Stanford, CA 94305, USA; VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
14
Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: wilsonp@uchicago.edu.

Abstract

Influenza is a leading cause of death in the elderly, and the vaccine protects only a fraction of this population. A key aspect of antibody-mediated anti-influenza virus immunity is adaptation to antigenically distinct epitopes on emerging strains. We examined factors contributing to reduced influenza vaccine efficacy in the elderly and uncovered a dramatic reduction in the accumulation of de novo immunoglobulin gene somatic mutations upon vaccination. This reduction is associated with a significant decrease in the capacity of antibodies to target the viral glycoprotein, hemagglutinin (HA), and critical protective epitopes surrounding the HA receptor-binding domain. Immune escape by antigenic drift, in which viruses generate mutations in key antigenic epitopes, becomes highly exaggerated. Because of this reduced adaptability, most B cells activated in the elderly cohort target highly conserved but less potent epitopes. Given these findings, vaccines driving immunoglobulin gene somatic hypermutation should be a priority to protect elderly individuals.

KEYWORDS:

elderly population; immunoglobulin genes; influenza vaccine; monoclonal antibodies

PMID:
30795982
PMCID:
PMC6452894
[Available on 2020-03-13]
DOI:
10.1016/j.chom.2019.01.002

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