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Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals
Open accessPreprint — published as 10.1016/j.cell.2022.01.027
Abstract
SUMMARY: Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. In this study, through a fine-needle-aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant (KTX) recipients. We found that, unlike healthy subjects, KTX recipients presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cells, SARS-CoV-2 receptor-binding-domain-specific memory B cells and neutralizing antibodies. KTX recipients also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals, and suggest a GC-origin for certain humoral and memory B cell responses following mRNA vaccination.
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“mRNA vaccines induce robust germinal center responses in humans (14, 15), which result in memory B cells that are specific for both the full-length SARS-CoV-2 spike protein and the spike receptor-binding domain (RBD) (16–18).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [15]
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Metadata
- Authors
- Lederer, K., Parvathaneni, K., Painter, M. M., Bettini, E., Agarwal, D., Lundgreen, K. A., Weirick, M., Goel, R. R., Xu, X., Drapeau, E. M., Gouma, S., Greenplate, A. R., Coz, C. L., Romberg, N., Jones, L., Rosen, M., Besharatian, B., Kaminiski, M., Weiskopf, D., Sette, A., Hensley, S. E., Bates, P., Wherry, E. J., Naji, A., Bhoj, V., & Locci, M.
- Affiliations
- University of Pennsylvania (US)
- Harvard University (US)
- Children's Hospital of Philadelphia (US)
- La Jolla Institute for Immunology (US)
- Corresponding author
- Naji, Ali
- Bhoj, Vijay
- Locci, Michela
- ORCID
- Lederer, Katlyn
- Parvathaneni, Kalpana
- Painter, Mark M.
- Bettini, Emily
- Agarwal, Divyansh
- Lundgreen, Kendall A.
- Weirick, Madison
- Goel, Rishi R.
- Drapeau, Elizabeth M.
- Gouma, Sigrid
- Greenplate, Allison R.
- Coz, Carole Le
- Romberg, Neil
- Besharatian, Behdad
- Weiskopf, Daniela
- Sette, Alessandro
- Hensley, Scott E.
- Bates, Paul
- Wherry, E. John
- Naji, Ali
- Bhoj, Vijay
- Locci, Michela
- Venue
- Cell
- Publisher
- openRxiv
- Published
- 2021-09-21
- Volume
- 185
- Issue
- 6
- Pages
- 1008-1024.e15
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8475965
- OpenAlex
- W4221071417
- Cited by
- 179
- References
- 0
- Citations by year
- 2026: 15 · 2025: 33 · 2024: 33 · 2023: 45 · 2022: 44 · 2021: 9
- FWCI
- 19.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repository University of Antioquia (University of Antioquia) (publishedVersion, cc-by)
- PubMed Central (submittedVersion)
- Funders
- National Institutes of Health (Nr. 75N9301900065, 75N9301900065)
- National Blood Foundation
- National Institute of Allergy and Infectious Diseases (R21AI142638, R01AI152236, R01AI146101, R01AI146026, R01AI123738, 75N9301900065, U19AI082630, R01AI153064)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- germinal center, COVID-19 mRNA vaccine, immunocompromised patients, kidney transplant recipients, memory B cells, T follicular helper cells, neutralizing antibodies, vaccine-induced immunity, humoral immunity, CD4 and CD8 T cells, lymph node fine needle aspiration
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