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.
Original language | English (US) |
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Pages (from-to) | 357-366.e6 |
Journal | Cell Host and Microbe |
Volume | 25 |
Issue number | 3 |
DOIs | |
State | Published - Mar 13 2019 |
Externally published | Yes |
Keywords
- elderly population
- immunoglobulin genes
- influenza vaccine
- monoclonal antibodies
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Virology