PreprintCited by 179SARS-CoV-2 and COVID-19 ResearchT-cell and B-cell ImmunologyImmune responses and vaccinations

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Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

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Lederer, Katlyn, Parvathaneni, Kalpana, Painter, Mark M., Bettini, Emily, Agarwal, Divyansh, Lundgreen, Kendall A., Weirick, Madison, Goel, Rishi R., Xu, Xiaoming, Drapeau, Elizabeth M., Gouma, Sigrid, Greenplate, Allison R., Coz, Carole Le, Romberg, Neil, Jones, Lisa, Rosen, Mark, Besharatian, Behdad, Kaminiski, Mary, Weiskopf, Daniela, Sette, Alessandro, Hensley, Scott E., Bates, Paul, Wherry, E. John, Naji, Ali, Bhoj, Vijay, Locci, Michela·2021·Cell

DOI 10.1101/2021.09.16.21263686PMC PMC8475965

Preprint — published as 10.1016/j.cell.2022.01.027

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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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10.1016/j.immuni.2020.06.001pmid:32561270 · DOI
10.1056/NEJMoa2027906 · DOI · Paper page

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“Because SARS-CoV-2 nucleoside-modified mRNA-LNP vaccines promote robust GC B cell and Tfh cell responses in humans (Lederer et al., 2021; Mudd et al., 2021; Turner et al., 2021), we argue that a similar pro-Tfh cellinducing activity is also present in humans and that the mechanism could also likely…”
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“SARSCoV-2 spike-specific circulating follicular helper T (cTfh) cells were measured at all time points (Figures 3C and S2D), as this subpopulation of CD4 T cells is crucial for supporting antibody responses following vaccination (Crotty, 2019; Lederer et al., 2022; Mudd et al., 2022).”
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See all 179

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)
DOI: 10.1101/2021.09.16.21263686
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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Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

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