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Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies
Open accessAbstract
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.
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“In view of the critical role played by CD4 + T cells in orchestrating the immune response, some of the age-related deficiencies observed in B cells (51,53,54), which include a reduction in the number of plasmablasts that develop in response to influenza vaccination (55) and the production of poor-quality antibodies to carbohydrate antigens (56)(57)(58), may occur secondary to T cell deficiencies.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [55]
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Metadata
- Authors
- Sasaki, S., Sullivan, M., Narvaez, C. F., Holmes, T. H., Furman, D., Zheng, N.-Y., Nishtala, M., Wrammert, J., Smith, K., James, J. A., Dekker, C. L., Davis, M. M., Wilson, P. C., Greenberg, H. B., & He, X.-S.
- Affiliations
- Stanford Medicine (US)
- University of Chicago (US)
- Emory University (US)
- Oklahoma Medical Research Foundation (US)
- Stanford University (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2011-08-01
- Volume
- 121
- Issue
- 8
- Pages
- 3109-3119
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3148747
- OpenAlex
- W2105359173
- Cited by
- 300
- References
- 52
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 8 · 2023: 21 · 2022: 18 · 2021: 33 · 2020: 15 · 2019: 26 · 2018: 15 · 2017: 22 · 2016: 18 · 2015: 20 · 2014: 19 · 2013: 27 · 2012: 25
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI090023, AI057266, AI057229, DK56339)
- National Institute of Allergy and Infectious Diseases (AI 057229, AI057158, U19AI090023, U19AI090019, AI057266, HHSN266200500026C, AI090023, U54AI057158, U19AI057229, U19AI057266)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-56339, P30DK056339)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR053483)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- inactivated influenza vaccine, vaccine efficacy, older adults, plasmablasts, antibody avidity, antibody affinity, 2009 H1N1 pandemic, cross-reactivity, exposure history, B cells, monoclonal antibodies
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Antibodies, Antibodies, Monoclonal, Antibody Affinity, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin A, Immunoglobulin G, Influenza, Human, Influenza Vaccines, Plasma Cells, Young Adult
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