An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.

A response to this article was published:

• Heaton, Penny M. 2020. "The Covid-19 Vaccine-Development Multiverse." New England Journal of Medicine 383 (20):1986-8.

A related article to this article was published:

• Anderson, Evan J., Nadine G. Rouphael, Alicia T. Widge, Lisa A. Jackson, Paul C. Roberts, Mamodikoe Makhene, James D. Chappell, Mark R. Denison, Laura J. Stevens, Andrea J. Pruijssers, Adrian B. McDermott, Britta Flach, Bob C. Lin, Nicole A. Doria-Rose, Sijy O’Dell, Stephen D. Schmidt, Kizzmekia S. Corbett, Phillip A. Swanson, Marcelino Padilla, Kathy M. Neuzil, Hamilton Bennett, Brett Leav, Mat Makowski, Jim Albert, Kaitlyn Cross, Venkata Viswanadh Edara, Katharine Floyd, Mehul S. Suthar, David R. Martinez, Ralph Baric, Wendy Buchanan, Catherine J. Luke, Varun K. Phadke, Christina A. Rostad, Julie E. Ledgerwood, Barney S. Graham, and John H. Beigel. 2020. "Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults." New England Journal of Medicine 383 (25):2427-38.
• Widge, Alicia T., Nadine G. Rouphael, Lisa A. Jackson, Evan J. Anderson, Paul C. Roberts, Mamodikoe Makhene, James D. Chappell, Mark R. Denison, Laura J. Stevens, Andrea J. Pruijssers, Adrian B. McDermott, Britta Flach, Bob C. Lin, Nicole A. Doria-Rose, Sijy O’Dell, Stephen D. Schmidt, Kathleen M. Neuzil, Hamilton Bennett, Brett Leav, Mat Makowski, Jim Albert, Kaitlyn Cross, Venkata-Viswanadh Edara, Katharine Floyd, Mehul S. Suthar, Wendy Buchanan, Catherine J. Luke, Julie E. Ledgerwood, John R. Mascola, Barney S. Graham, and John H. Beigel. 2020. "Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination." New England Journal of Medicine 384 (1):80-2.
  
  

Jackson, Lisa A., Evan J. Anderson, Nadine G. Rouphael, Paul C. Roberts, Mamodikoe Makhene, Rhea N. Coler, Michele P. McCullough, James D. Chappell, Mark R. Denison, Laura J. Stevens, Andrea J. Pruijssers, Adrian McDermott, Britta Flach, Nicole A. Doria-Rose, Kizzmekia S. Corbett, Kaitlyn M. Morabito, Sijy O’Dell, Stephen D. Schmidt, Phillip A. Swanson, Marcelino Padilla, John R. Mascola, Kathleen M. Neuzil, Hamilton Bennett, Wellington Sun, Etza Peters, Mat Makowski, Jim Albert, Kaitlyn Cross, Wendy Buchanan, Rhonda Pikaart-Tautges, Julie E. Ledgerwood, Barney S. Graham, and John H. Beigel.

2020-07-14

Jackson, Lisa A., Evan J. Anderson, Nadine G. Rouphael, Paul C. Roberts, Mamodikoe Makhene, Rhea N. Coler, Michele P. McCullough, James D. Chappell, Mark R. Denison, Laura J. Stevens, Andrea J. Pruijssers, Adrian McDermott, Britta Flach, Nicole A. Doria-Rose, Kizzmekia S. Corbett, Kaitlyn M. Morabito, Sijy O’Dell, Stephen D. Schmidt, Phillip A. Swanson, Marcelino Padilla, John R. Mascola, Kathleen M. Neuzil, Hamilton Bennett, Wellington Sun, Etza Peters, Mat Makowski, Jim Albert, Kaitlyn Cross, Wendy Buchanan, Rhonda Pikaart-Tautges, Julie E. Ledgerwood, Barney S. Graham, and John H. Beigel. 2020. "An mRNA Vaccine against SARS-CoV-2 — Preliminary Report." New England Journal of Medicine.

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.

Methods

We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group.

Results

After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.

Conclusions

The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461. opens in new tab).

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