Low dose mRNA-1273 COVID-19 vaccine generates durable T cell memory and antibodies enhanced by pre-existing crossreactive T cell memory
Open accessPreprint — published as 10.1126/science.abj9853
Abstract
Understanding human immune responses to SARS-CoV-2 RNA vaccines is of interest for a panoply of reasons. Here we examined vaccine-specific CD4 + T cell, CD8 + T cell, binding antibody, and neutralizing antibody responses to the 25 μg Moderna mRNA-1273 vaccine over 7 months post-immunization, including multiple age groups, with a particular interest in assessing whether pre-existing crossreactive T cell memory impacts vaccine-generated immunity. Low dose (25 μg) mRNA-1273 elicited durable Spike binding antibodies comparable to that of convalescent COVID-19 cases. Vaccine-generated Spike memory CD4 + T cells 6 months post-boost were comparable in quantity and quality to COVID-19 cases, including the presence of T FH cells and IFNγ-expressing cells. Spike CD8 + T cells were generated in 88% of subjects, with equivalent percentages of CD8 + T cell memory responders at 6 months post-boost compared to COVID-19 cases. Lastly, subjects with pre-existing crossreactive CD4 + T cell memory had increased CD4 + T cell and antibody responses to the vaccine, demonstrating a biological relevance of SARS-CoV-2 crossreactive CD4 + T cells. One-Sentence Summary: The mRNA-1273 vaccine induces a durable and functional T cell and antibody response comparable to natural infection.
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mRNA vaccination generates spike-specific memory CD4+ and CD8+ T cell responses.
“mRNA vaccination has also been shown to generate spike-specific memory CD4+ and CD8+ T cell responses (19–22).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [22]
SARS-CoV-2 mRNA vaccination efficiently primed antigen-specific CD4+ T cells and CD8+ T cells.
“Consistent with recent studies, SARS-CoV-2 mRNA vaccination efficiently primed antigen-specific CD4+ T cells and CD8+ T cells (Fig. 5, C and D) (20–22).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [22]
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mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern
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- Authors
- Mateus, J., Dan, J. M., Zhang, Z., Moderbacher, C. R., Lammers, M., Goodwin, B., Sette, A., Crotty, S., & Weiskopf, D.
- Affiliations
- La Jolla Institute for Immunology (US)
- Corresponding author
- Sette, Alessandro
- Crotty, Shane
- Weiskopf, Daniela
- ORCID
- Venue
- Science
- Publisher
- openRxiv
- Published
- 2021-07-05
- Volume
- 374
- Issue
- 6566
- Pages
- eabj9853-eabj9853
- ISSN
- 0036-8075 (ISSN-L)
- PMC
- PMC8542617
- OpenAlex
- W3199923482
- Cited by
- 327
- References
- 3
- Citations by year
- 2026: 12 · 2025: 41 · 2024: 48 · 2023: 76 · 2022: 121 · 2021: 29
- FWCI
- 21.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by)
- Funders
- Emory University
- National Institutes of Health (Nr. 75N9301900065, HHSN272201500002C, 75N9301900065, OD011132, AI 142742, AI149644, P51OD011132)
- National Institute of Allergy and Infectious Diseases (K08AI135078, AI135078, U01AI149644, AI149644, R01AI135193, 75N9301900065, HHSN272201500002C, NIH AID AI149644, AI142742, UM1AI148373, U19AI142742, UM1AI148576, R25AI147376, UM1AI148684)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- mRNA-1273 vaccine, COVID-19 vaccines, low-dose vaccination, SARS-CoV-2, T cell immunity, memory T cells, cross-reactive T cells, vaccine dose comparison, vaccine reactogenicity, antibody response, older adults
- MeSH terms
- Immunogenicity, Vaccine, COVID-19, COVID-19 Vaccines, 2019-nCoV Vaccine mRNA-1273, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Viral, Cross Reactions, Humans, Immunologic Memory, Middle Aged, Vaccination, CD4-Positive T-Lymphocytes, Clinical Trials, Phase I as Topic, CD8-Positive T-Lymphocytes, Young Adult, Spike Glycoprotein, Coronavirus
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