Circulating CXCR5+PD-1+ Response Predicts Influenza Vaccine Antibody Responses in Young Adults but not Elderly Adults
Open accessAbstract
Although influenza vaccination is recommended for all adults annually, the incidence of vaccine failure, defined as weak or absent increase in neutralizing Ab titers, is increased in the elderly compared with young adults. The T follicular helper cell (Tfh) subset of CD4 T cells provides B cell help in germinal centers and is necessary for class-switched Ab responses. Previous studies suggested a role for circulating Tfh cells (cTfh) following influenza vaccination in adults, but cTfh have not been studied in elderly adults in whom weak vaccine responses are often observed. In this study, we studied cTfh expressing CXCR5 and programmed death-1 (PD-1). cTfh from elderly adults were present at reduced frequency, had decreased in vitro B cell help ability, and had greater expression of ICOS compared with young adults. At 7 d after inactivated influenza vaccination, cTfh correlated with influenza vaccine–specific IgM and IgG responses in young adults but not in elderly adults. In sum, we have identified aging-related changes in cTfh that correlated with reduced influenza vaccine responses. Future rational vaccine design efforts should incorporate Tfh measurement as an immune correlate of protection, particularly in the setting of aging.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Timepoints were chosen a priori to capture the peak antigen-specific response for primary and secondary responses in SARS-CoV-2 naïve individuals.
“Timepoints were chosen a priori to capture the peak antigen-specific response for primary (41) and secondary responses (42, 43) in SARS-CoV-2 naïve individuals.”
From Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals after mRNA vaccination (2021) · cites this paper as [43]
After vaccination, T follicular helper cells are less frequent in older subjects and appear to malfunction.
“after vaccination, T follicular helper (Tfh) cells are less frequent in older subjects and appear to be malfunctioning”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Herati et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 65 · Cited by 177
Research works printed but not linked: 1
- [39]WHO Global Influenza Surveillance Network Network S 2011 Manual for the laboratory diagnosis and virological surveillance of influenza WHO Press Geneva, Switzerland
- Authors
- Herati, R. S., Reuter, M. A., Dolfi, D. V., Mansfield, K. D., Aung, H., Badwan, O. Z., Kurupati, R. K., Kannan, S., Ertl, H., Schmader, K. E., Betts, M. R., Canaday, D. H., & Wherry, E. J.
- Affiliations
- University of Pennsylvania (US)
- Janssen Research & Development (United States) (US)
- Louis Stokes Cleveland VA Medical Center (US)
- Division of Infectious Disease, Case Western Reserve University , Cleveland, OH 44106
- The Wistar Institute (US)
- Duke University (US)
- Corresponding author
- Wherry, E John
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10-01
- Volume
- 193
- Issue
- 7
- Pages
- 3528-3537
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC4170011
- OpenAlex
- W1957514873
- Cited by
- 177
- References
- 65
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 9 · 2023: 20 · 2022: 12 · 2021: 24 · 2020: 20 · 2019: 19 · 2018: 12 · 2017: 19 · 2016: 10 · 2015: 7 · 2014: 1
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG028716, P30AG028716)
- National Institute of Allergy and Infectious Diseases (HHSN266200500030C, AI080313, AI36219, T32AI007632, R01AI076066, R01AI080313, R01AI108972, P30AI036219, P30AI045008)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- CXCR5, PD-1, influenza vaccination, vaccine antibody response, vaccine failure, aging, older adults, ICOS, B cell help, germinal center, class switch recombination, correlates of protection
- MeSH terms
- Adult, Age Factors, Aging, Antibodies, Viral, Antibody Formation, B-Lymphocytes, Female, Humans, Immunoglobulin G, Immunoglobulin M, Influenza Vaccines, Male, CD4-Positive T-Lymphocytes, Germinal Center, Receptors, CXCR5, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
