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

Carole Henry, Nai Ying Zheng, Min Huang, Alexandra Cabanov, Karla Thatcher Rojas, Kaval Kaur, Sarah F. Andrews, Anna Karin E. Palm, Yao Qing Chen, Yang Li, Katerina Hoskova, Henry A. Utset, Marcos C. Vieira, Jens Wrammert, Rafi Ahmed, Jeanne Holden-Wiltse, David J. Topham, John J. Treanor, Hildegund C. Ertl, Kenneth E. SchmaderSarah Cobey, Florian Krammer, Scott E. Hensley, Harry Greenberg, Xiaosong He, Patrick C. Wilson

Research output: Contribution to journalArticle

24 Scopus citations

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 languageEnglish (US)
Pages (from-to)357-366.e6
JournalCell Host and Microbe
Volume25
Issue number3
DOIs
StatePublished - Mar 13 2019
Externally publishedYes

Keywords

  • elderly population
  • immunoglobulin genes
  • influenza vaccine
  • monoclonal antibodies

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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  • Cite this

    Henry, C., Zheng, N. Y., Huang, M., Cabanov, A., Rojas, K. T., Kaur, K., Andrews, S. F., Palm, A. K. E., Chen, Y. Q., Li, Y., Hoskova, K., Utset, H. A., Vieira, M. C., Wrammert, J., Ahmed, R., Holden-Wiltse, J., Topham, D. J., Treanor, J. J., Ertl, H. C., ... Wilson, P. C. (2019). Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals. Cell Host and Microbe, 25(3), 357-366.e6. https://doi.org/10.1016/j.chom.2019.01.002