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.
Henry, C; Zheng, N-Y; Huang, M; Cabanov, A; Rojas, KT; Kaur, K; Andrews, SF; Palm, A-KE; Chen, Y-Q; Li, Y; Hoskova, K; Utset, HA; Vieira, MC; Wrammert, J; Ahmed, R; Holden-Wiltse, J; Topham, DJ; Treanor, JJ; Ertl, HC; Schmader, KE; Cobey, S; Krammer, F; Hensley, SE; Greenberg, H; He, X-S; Wilson, PC
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