Tweet
Cell Host Microbe. 2019 Jan 24. pii: S1931-3128(19)30039-3. doi: 10.1016/j.chom.2019.01.002. [Epub ahead of print]
Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals.
Henry C1, Zheng NY2, Huang M2, Cabanov A2, Rojas KT2, Kaur K2, Andrews SF2, Palm AE2, Chen YQ2, Li Y3, Hoskova K2, Utset HA2, Vieira MC4, Wrammert J5, Ahmed R6, Holden-Wiltse J7, Topham DJ8, Treanor JJ9, Ertl HC10, Schmader KE11, Cobey S4, Krammer F12, Hensley SE3, Greenberg H13, He XS13, Wilson PC14.
Author information
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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
elderly population; immunoglobulin genes; influenza vaccine; monoclonal antibodies
PMID: 30795982 DOI: 10.1016/j.chom.2019.01.002
Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals.
Henry C1, Zheng NY2, Huang M2, Cabanov A2, Rojas KT2, Kaur K2, Andrews SF2, Palm AE2, Chen YQ2, Li Y3, Hoskova K2, Utset HA2, Vieira MC4, Wrammert J5, Ahmed R6, Holden-Wiltse J7, Topham DJ8, Treanor JJ9, Ertl HC10, Schmader KE11, Cobey S4, Krammer F12, Hensley SE3, Greenberg H13, He XS13, Wilson PC14.
Author information
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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
elderly population; immunoglobulin genes; influenza vaccine; monoclonal antibodies
PMID: 30795982 DOI: 10.1016/j.chom.2019.01.002