Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates
Open accessAbstract
Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 – 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP. One-Sentence Summary: mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.
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Many nucleoside-modified mRNA COVID-19 vaccines, including BNT162b2, BNT162b1, BNT162b3, mRNA-1273, TAK919, mRNA-1273.211, mRNA-1273.351, mRNA-1283, ChulaCov19, and PTX-COVID19-B, have been approved for commercialization or entered clinical trials.
“Many nucleoside-modified mRNA COVID-19 vaccines, including BNT162b2, BNT162b1, and BNT162b3 developed by BioNTech27,177; mRNA-1273, TAK919, mRNA-1273.211, mRNA-1273.351, mRNA-1283 developed by Moderna28,178; ChulaCov19 developed by Chulalongkorn University; and PTX-COVID19-B developed by Providence Therapeutics, have been approved for commercialization or entered clinical trials.104”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [178]
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- Authors
- Corbett, K. S., Nason, M. C., Flach, B., Gagne, M., O’ Connell, S., Johnston, T. S., Shah, S. N., Edara, V. V., Floyd, K., Lai, L., McDanal, C., Francica, J. R., Flynn, B., Wu, K., Choi, A., Koch, M., Abiona, O. M., Werner, A. P., Alvarado, G. S., Andrew, S. F., Donaldson, M. M., Fintzi, J., Flebbe, D. R., Lamb, E., Noe, A. T., Nurmukhambetova, S. T., Provost, S. J., Cook, A., Dodson, A., Faudree, A., Greenhouse, J., Kar, S., Pessaint, L., Porto, M., Steingrebe, K., Valentin, D., Zouantcha, S., Bock, K. W., Minai, M., Nagata, B. M., Moliva, J. I., van de Wetering, R., Boyoglu-Barnum, S., Leung, K., Shi, W., Yang, E. S., Zhang, Y., Todd, J.-P. M., Wang, L., Andersen, H., Foulds, K. E., Edwards, D. K., Mascola, J. R., Moore, I. N., Lewis, M. G., Carfi, A., Montefiori, D., Suthar, M. S., McDermott, A., Sullivan, N. J., Roederer, M., Douek, D. C., Graham, B. S., & Seder, R. A.
- Affiliations
- National Institutes of Health (US)
- Emory University (US)
- Duke Medical Center (US)
- Bioqual (US)
- Corresponding author
- Graham, Barney S.
- Seder, Robert A.
- ORCID
- Corbett, Kizzmekia S.
- Nason, Martha C.
- Johnston, Timothy S.
- Shah, Shruti N.
- Edara, Venkata Viswanadh
- Floyd, Katharine
- Lai, Lilin
- McDanal, Charlene
- Francica, Joseph R.
- Flynn, Barbara
- Choi, Angela
- Abiona, Olubukola M.
- Werner, Anne P.
- Alvarado, Gabriela S.
- Andrew, Shayne F.
- Fintzi, Jonathan
- Lamb, Evan
- Noe, Amy T.
- Provost, Samantha J.
- Cook, Anthony
- Dodson, Alan
- Faudree, Andrew
- Greenhouse, Jack
- Kar, Swagata
- Pessaint, Laurent
- Porto, Maciel
- Steingrebe, Katelyn
- Bock, Kevin W.
- Minai, Mahnaz
- Nagata, Bianca M.
- Moliva, Juan I.
- Leung, Kwanyee
- Shi, Wei
- Yang, Eun Sung
- Zhang, Yi
- Todd, John-Paul M.
- Wang, Lingshu
- Foulds, Kathryn E.
- Edwards, Darin K.
- Mascola, John R.
- Moore, Ian N.
- Lewis, Mark G.
- Montefiori, David
- Suthar, Mehul S.
- McDermott, Adrian
- Sullivan, Nancy J.
- Roederer, Mario
- Douek, Daniel C.
- Graham, Barney S.
- Seder, Robert A.
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2021-04-21
- PMC
- PMC8077626
- OpenAlex
- W3156468949
- Cited by
- 43
- References
- 55
- Citations by year
- 2023: 3 · 2022: 8 · 2021: 32
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- U.S. Department of Energy (COVID-19)
- U.S. Department of Health and Human Services (75A50120C00034)
- Emory University
- Children's Healthcare of Atlanta
- National Institutes of Health (COVID-19, 75A50120C00034)
- Oak Ridge Institute for Science and Education
- Biomedical Advanced Research and Development Authority (75A50120C00034)
- NIH Office of the Director
- National Institute of Allergy and Infectious Diseases (COVID-19, 75A50120C00034)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- correlates of protection, mRNA-1273 vaccine, SARS-CoV-2, nonhuman primate model, humoral immune response, neutralizing antibodies, antibody binding, viral replication
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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