Preliminary results are in for several experimental vaccines to protect against SARS-CoV-2, the virus that causes COVID-19. One vaccine in development by the NIAID Vaccine Research Center and ModernaTX, Inc., appears to stimulate robust immune responses in healthy adults without serious safety concerns, according to data published in The New England Journal of Medicine on July 14.
“Our results show that the vaccine induces a robust neutralizing antibody response in healthy volunteers, which looks similar to responses in people who had COVID-19,” said James Chappell, M.D., who directs vaccine and antibody studies in the Denison laboratory at Vanderbilt University Medical Center.
Vanderbilt researchers are contributing to the NIAID mRNA-1273 Study Group that published the findings. Vanderbilt’s team also includes coronavirus expert Mark Denison, M.D., Edward Claiborne Stahlman Professor of Pediatrics and director of the Division of Pediatric Infectious Diseases; Laura Stevens; Andrea Pruijssers, Ph.D.; Tia Hughes and Xiaotao Lu.
“Our results show that the vaccine induces a robust neutralizing antibody response in healthy volunteers, which looks similar to responses in people who had COVID-19.”
The phase 1, dose-escalation, open-label trial tested the safety and immunogenicity of mRNA-1273. The mRNA encodes the full-length, stabilized prefusion SARS-CoV-2 spike (or “crown”) protein, encapsulated in a novel lipid nanoparticle.
Forty-five healthy adults aged 18 to 55 participated. The vast majority (40 participants, or 89 percent) identified as white. All but three participants¹ received two identical vaccinations 28 days apart. Participants were split evenly across three dose groups and received either 25, 100 or 250μg of mRNA-1273 at each vaccination. The report includes data from the first 57 days of the trial.
A Robust Response
The candidate vaccine appeared quite immunogenic. In all participants, researchers found antibodies to both full-length SARS-CoV-2 spike protein and its receptor binding domain soon after the first vaccination. Seroconversion occurred within two weeks. The antibody responses were time- and dose-dependent.
Vanderbilt researchers compared study participant immune responses to those induced by SARS-CoV-2 infection by also analyzing 41 convalescent serum samples.
The preliminary report includes specific antibody titers, pseudovirus and live virus neutralizing responses, and CD4 T-cell counts. The authors noted “pseudovirus neutralizing activity was low before the second vaccination, which supports the need for a two-dose vaccination schedule.”
“Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site,” wrote the authors. “Systemic adverse events were more common after the second vaccination, particularly with the highest dose.” One participant in the highest dose group experienced a 39.6°C fever after the second vaccination. The authors noted the safety profile appears similar to that of another, related mRNA vaccine in development.
Though more than half of participants reported some adverse event, when present, nearly all events were mild or moderate. The researchers reported “no patterns of concern.”
A Rapid Timeline
The candidate vaccine’s development has moved at unprecedented speed – just 66 days. Wrote the authors, “Vaccine development was initiated after the SARS-CoV-2 genome was posted on January 10, 2020; manufacture and delivery of clinical trials material was completed within 45 days, and the first trial participants were vaccinated on March 16, 2020.”
More results are expected soon, as the researchers added study groups to the protocol based on their interim analyses. They also plan to follow all participants for a full year to track durability of immune responses.
In the meantime, a phase 2 trial is already underway and a larger phase 3 trial is slated to start this summer.