The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses
Open accessAbstract
T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.
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In the citing paper
“BNT162b2 is based on lipid-nanoparticle-formulated mRNA vaccine technology, which delivers precise genetic information of the immunogen to antigen-presenting cells and elicits potent immune responses 7 .”
From BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans (2021) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The rapid and robust immunogenicity profile of the mRNA-1273 vaccine most likely results from an innovative structure-based vaccine antigen design,23 coupled with a potent lipid-nanoparticle delivery system, and the use of modified nucleotides that avoid early intracellular activation of interferon-associated genes.”
From An mRNA Vaccine against SARS-CoV-2 — Preliminary Report (2020) · cites this paper as [24]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“These features of the mRNA composition and formulation have been associated with prolonged protein expression, induction of antigen-specific T-follicular helper cells, and activation of germinal center B cells.24”
From An mRNA Vaccine against SARS-CoV-2 — Preliminary Report (2020) · cites this paper as [24]
In the citing paper
“Thus, in agreement with previous results (13, 25, 26), mRNA-1273 vaccination induces TH1- and TFH-skewed CD4 T cell responses.”
From Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates (2021) · cites this paper as [26]
In the citing paper
“In contrast, Pardi and colleagues reported that protein levels after intradermal injection of m1ψ-modified mRNA in mice were 20 times higher compared to sequence-optimized but unmodified mRNA.184”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [184]
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 [54]
In the citing paper
“One study in mice showed that LNPs encapsulating nucleoside-modified mRNA circulated for longer and induced stronger TFH cell and germinal centre B cell responses than LNPs carrying unmodified mRNA200.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [200]
In the citing paper
“several studies have shown that i.m. delivery of 1mΨ-modified mRNA vaccines results in the rapid and potent induction of follicular T helper cells (Tfh) [71,72].”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [72]
In the citing paper
“Lipid nanoparticle–mRNA vaccines are also being investigated as influenza vaccines29,41,156,157,159,184,189–191, with some formulations in clinical trials (Table 1).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [190]
In the citing paper
“Lipid nanoparticle–mRNA formulations are further being explored for Zika virus vaccines38,190,192–194.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [190]
In the citing paper
“Furthermore, lipid nanoparticle–mRNA vaccines have been tested against other viruses in animal models, including human immunodeficiency virus28,144,181,190, Powassan virus195, Venezuelan equine encephalitis virus196, dengue virus73 and Ebola virus197.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [190]
In the citing paper
“Additionally, the robust and sustained antigen expression of nucleoside-modified mRNA was associated with more optimal antibody responses compared to unmodified mRNA [12,13].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [12]
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Citations
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Metadata
- Authors
- Pardi, N., Hogan, M. J., Naradikian, M. S., Parkhouse, K., Cain, D. W., Jones, L., Moody, M. A., Verkerke, H. P., Myles, A., Willis, E., LaBranche, C. C., Montefiori, D. C., Lobby, J. L., Saunders, K. O., Liao, H.-X., Korber, B. T., Sutherland, L. L., Scearce, R. M., Hraber, P. T., Tombácz, I., Muramatsu, H., Ni, H., Balikov, D. A., Li, C., Mui, B. L., Tam, Y. K., Krammer, F., Karikó, K., Polacino, P., Eisenlohr, L. C., Madden, T. D., Hope, M. J., Lewis, M. G., Lee, K. K., Hu, S.-L., Hensley, S. E., Cancro, M. P., Haynes, B. F., & Weissman, D.
- Affiliations
- University of Pennsylvania (US)
- Duke University (US)
- University of Washington (US)
- Duke Medical Center (US)
- Children's Hospital of Philadelphia (US)
- Los Alamos National Laboratory (US)
- Department of Medicine, University of Pennsylvania, Philadelphia, PA 1
- Acuitas Therapeutics (Canada) (CA)
- Icahn School of Medicine at Mount Sinai (US)
- BioNTech (Germany) (DE)
- Bioqual (US)
- Corresponding author
- Weissman, Drew
- ORCID
- Pardi, Norbert
- Hogan, Michael J.
- Naradikian, Martin S.
- Parkhouse, Kaela
- Cain, Derek W.
- Jones, Letitia
- Moody, M. Anthony
- Verkerke, Hans P.
- Willis, Elinor
- LaBranche, Celia C.
- Montefiori, David C.
- Lobby, Jenna L.
- Saunders, Kevin O.
- Liao, Hua-Xin
- Korber, Bette T.
- Sutherland, Laura L.
- Scearce, Richard M.
- Hraber, Peter T.
- Tombácz, István
- Muramatsu, Hiromi
- Ni, Houping
- Balikov, Daniel A.
- Mui, Barbara L.
- Tam, Ying K.
- Krammer, Florian
- Karikó, Katalin
- Eisenlohr, Laurence C.
- Lewis, Mark G.
- Lee, Kelly K.
- Hu, Shiu-Lok
- Hensley, Scott E.
- Cancro, Michael P.
- Haynes, Barton F.
- Weissman, Drew
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2018-05-08
- Volume
- 215
- Issue
- 6
- Pages
- 1571-1588
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC5987916
- OpenAlex
- W2802953285
- Cited by
- 530
- References
- 56
- Citations by year
- 2026: 58 · 2025: 51 · 2024: 77 · 2023: 65 · 2022: 93 · 2021: 118 · 2020: 40 · 2019: 22 · 2018: 6
- FWCI
- 19.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- National Institutes of Health (5T32AI055428-12, U19 AI109946-01, 5R01GM099989-04)
- U.S. Department of Defense (PR130769)
- National Institute of Allergy and Infectious Diseases (R01-AI050484, R01-AI124429, R01-AI084860, HHSN27201100016C)
- Gates Foundation (CAVD 0PP1033102, CAVD OPP1033102)
- Takeda Pharmaceuticals U.S.A
- Center for Global Health (OPP1126258)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- nucleoside-modified mRNA, mRNA vaccines, lipid nanoparticles, T follicular helper cells, germinal center B cells, intradermal vaccination, neutralizing antibodies, affinity maturation, memory B cells, viral surface antigens, non-human primates, vaccine adjuvants
- MeSH terms
- Adjuvants, Immunologic, Animals, Antibody Formation, Antigens, B-Lymphocytes, T-Lymphocytes, Helper-Inducer, Lipids, Macaca mulatta, Nucleosides, RNA, Messenger, Time Factors, Vaccination, Germinal Center, Protein Subunits, Vaccines, Subunit, Nanoparticles, Antibodies, Neutralizing
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