Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies

Sanae Sasaki, Meghan Sullivan, Carlos F. Narvaez, Tyson H. Holmes, David Furman, Nai Ying Zheng, Madhuri Nishtala, Jens Wrammert, Kenneth Smith, Judith A. James, Cornelia L. Dekker, Mark M. Davis, Patrick C. Wilson, Harry B. Greenberg, Xiaosong He

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies.

Original languageEnglish (US)
Pages (from-to)3109-3119
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number8
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

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Inactivated Vaccines
Influenza Vaccines
Vaccines
Antibodies
Antibody Affinity
Human Influenza
Antibody Formation
Young Adult
Vaccination
Monoclonal Antibodies
Enzyme-Linked Immunospot Assay
H1N1 Subtype Influenza A Virus
Pandemics
Cultured Cells
Immunization
B-Lymphocytes
Age Groups
Immunoglobulin G
History
Serum

ASJC Scopus subject areas

  • Medicine(all)

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Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. / Sasaki, Sanae; Sullivan, Meghan; Narvaez, Carlos F.; Holmes, Tyson H.; Furman, David; Zheng, Nai Ying; Nishtala, Madhuri; Wrammert, Jens; Smith, Kenneth; James, Judith A.; Dekker, Cornelia L.; Davis, Mark M.; Wilson, Patrick C.; Greenberg, Harry B.; He, Xiaosong.

In: Journal of Clinical Investigation, Vol. 121, No. 8, 01.08.2011, p. 3109-3119.

Research output: Contribution to journalArticle

Sasaki, S, Sullivan, M, Narvaez, CF, Holmes, TH, Furman, D, Zheng, NY, Nishtala, M, Wrammert, J, Smith, K, James, JA, Dekker, CL, Davis, MM, Wilson, PC, Greenberg, HB & He, X 2011, 'Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies', Journal of Clinical Investigation, vol. 121, no. 8, pp. 3109-3119. https://doi.org/10.1172/JCI57834
Sasaki, Sanae ; Sullivan, Meghan ; Narvaez, Carlos F. ; Holmes, Tyson H. ; Furman, David ; Zheng, Nai Ying ; Nishtala, Madhuri ; Wrammert, Jens ; Smith, Kenneth ; James, Judith A. ; Dekker, Cornelia L. ; Davis, Mark M. ; Wilson, Patrick C. ; Greenberg, Harry B. ; He, Xiaosong. / Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 8. pp. 3109-3119.
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