Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals.
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.
Duke Scholars
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Related Subject Headings
- Young Adult
- Orthomyxoviridae
- Mutation
- Middle Aged
- Influenza Vaccines
- Immunology
- Immunity, Humoral
- Humans
- Healthy Volunteers
- Epitopes
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Young Adult
- Orthomyxoviridae
- Mutation
- Middle Aged
- Influenza Vaccines
- Immunology
- Immunity, Humoral
- Humans
- Healthy Volunteers
- Epitopes