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

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


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / immunology*
  • Epitopes / genetics
  • Epitopes / immunology*
  • Healthy Volunteers
  • Humans
  • Immunity, Humoral*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Middle Aged
  • Mutation
  • Orthomyxoviridae / genetics
  • Orthomyxoviridae / immunology*
  • Young Adult


  • Epitopes
  • Influenza Vaccines