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SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation
Open accessAbstract
The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms-mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant-looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses.
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“Our data in humans corroborate reports that demonstrate the induction of potent germinal centre responses by SARS-CoV-2 mRNA-based vaccines in mice22,23.”
From SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses (2021) · cites this paper as [23]
In the citing paper
“Indeed, a persistent antigen-specific germinal center B cell response and plasmablast response in blood and draining lymph nodes are elicited after vaccination with SARS-CoV-2 LNP-mRNA in humans, leading to the development of a robust and prolonged humoral immunity.53,58”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [53]
In the citing paper
“The germinal center B cell response and its regulation by CD4+ T follicular helper (Tfh) cells are of key importance for high-affinity neutralization antibody titers and long-lasting B cell responses.53,54”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [53]
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“in which their absolute numbers correlated with the levels of neutralizing antibodies [74].”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [74]
In the citing paper
“Pardi and colleagues recently demonstrated that a single immunization of mice with 1mΨ-modified mRNA LNP vaccines could elicit potent S-specific GC B cells and Tfh cells”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [74]
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InfluentialCutting Edge: Distinct Waves of BCL6 Expression during T Follicular Helper Cell Development
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MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer
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“A previously published study also described small GC formation by microscopy after one immunization with a protein antigen inMF59 (Liang et al., 2017).”
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Metadata
- Authors
- Lederer, K., Castaño, D., Gómez Atria, D., Oguin, T. H., Wang, S., Manzoni, T. B., Muramatsu, H., Hogan, M. J., Amanat, F., Cherubin, P., Lundgreen, K. A., Tam, Y. K., Fan, S. H. Y., Eisenlohr, L. C., Maillard, I., Weissman, D., Bates, P., Krammer, F., Sempowski, G. D., Pardi, N., & Locci, M.
- Affiliations
- University of Pennsylvania (US)
- Universidad de Antioquia (CO)
- Duke University (US)
- Children's Hospital of Philadelphia (US)
- Icahn School of Medicine at Mount Sinai (US)
- Acuitas Therapeutics (Canada) (CA)
- Corresponding author
- Locci, Michela
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 53
- Issue
- 6
- Pages
- 1281-1295.e5
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC7680029
- OpenAlex
- W3109969518
- Cited by
- 383
- References
- 65
- Citations by year
- 2026: 27 · 2025: 39 · 2024: 50 · 2023: 61 · 2022: 97 · 2021: 105 · 2020: 4
- FWCI
- 8.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repository University of Antioquia (University of Antioquia) (publishedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health
- 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
- SARS-CoV-2, COVID-19 vaccines, mRNA vaccines, recombinant protein vaccine, MF59 adjuvant, germinal center reaction, T follicular helper cells, long-lived plasma cells, memory B cells, neutralizing antibodies, B cell response, vaccine platform comparison
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, Epitopes, Antigens, Viral, B-Lymphocytes, Cells, Cultured, T-Lymphocytes, Helper-Inducer, Humans, Lymphocyte Activation, Polysorbates, Recombinant Proteins, RNA, Viral, Squalene, Vaccination, Vaccines, Synthetic, Germinal Center, Antibodies, Neutralizing
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