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 NY, Huang M, Cabanov A, Rojas KT, Kaur K, Andrews SF, Palm AE, Chen YQ, 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 XS, Wilson PC. (2019). Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals. Cell host & microbe, 25(3)