Background: mRNA-1273 was developed by Moderna based on prior studies of related coronaviruses such as those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A Phase 1 trial (NCT04283461) of 105 healthy participants provided the basis for Moderna’s investigational new drug application (IND), which was successfully reviewed by the FDA and set the stage for Phase 2 testing. A Phase 2 trial of 600 healthy participants evaluating 25 µg, 100 µg, and 250 µg dose levels of the vaccine was completed, and mRNA-1273 has advanced to a Phase 3 trial (NCT04405076).

Study Design: A Phase 3 trial of 30,000 participants at high risk for SARS-CoV-2 infection who will receive a 100 µg dose of mRNA-1273 or placebo and then followed for up to 2 years (COVE trial; NCT04470427).

Outcomes: Phase 1 data published in the New England Journal of Medicine showed mRNA-1273 successfully produced neutralizing antibody titers in 8 participants who received either 25 µg or 100 µg doses. The response was dose dependent in 45 participants across 25 µg, 100 µg, and 250 µg dose levels. In participants with available antibody data, neutralizing antibody titers were on par with what has been in seen in convalescent sera from people who have successfully fought off COVID-19. Results from a challenge in a mouse model showed mRNA-1273 prevented viral replication in the lungs, and neutralizing titers in the mouse model were similar in participants receiving 25 µg or 100 µg doses of the vaccine. Moderna said mRNA-1273 was "generally safe and well tolerated." A study of nonhuman primates challenged with SARS-CoV-2 published in the New England Journal of Medicine had neutralizing activity, and limited inflammation and lung activity after being administered the vaccine. A paper published in Nature also showed mRNA-1273 induced neutralizing antibodies in mice.

Status: On 12 May, the FDA granted Fast Track designation to mRNA-1273. A Phase 3 trial of the vaccine is underway, which is being funded by Operation Warp Speed.