VUMC studies provide key positive results for COVID-19 vaccine in early-stage clinical trial

Published on September 14th, 2020 by Diana Duren.

An experimental coronavirus vaccine stimulated robust immune responses against SARS-CoV-2, the virus that causes COVID-19, and raised no serious safety concerns in an early-stage clinical trial.

The vaccine, called mRNA-1273, was developed by Moderna Inc. in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Early findings from the phase 1 clinical trial of the vaccine, published in the New England Journal of Medicine, support further development of mRNA-1273. A large phase 3 clinical trial began in August.

Vaccines and therapeutics are urgently needed to slow the unrelenting COVID-19 pandemic, which has sickened more than 25 million people worldwide and killed at least 858,436 as of Sept. 2.

The phase 1 trial of mRNA-1273 enrolled 45 healthy volunteers ages 18 to 55, who received two vaccinations 28 days apart. The interim report includes follow-up through day 57; participants will continue to be followed for one year after the second vaccination, with scheduled blood collections to characterize immune responses.

The Vanderbilt University Medical Center research team led by coronavirus expert Mark Denison, MD, Edward Claiborne Stahlman Professor of Pediatrics and director of the Division of Pediatric Infectious Diseases, is a key contributor to the phase 1 trial testing. The researchers are analyzing the ability of antibodies in blood serum samples from trial participants to “neutralize” live SARS-CoV-2 and prevent the virus from infecting cultured cells.

“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 Jim Chappell, MD, PhD, research associate professor of Pediatrics and director of the vaccine and antibody studies in the Denison laboratory. “This work, in conjunction with the results of other laboratory studies at the NIH and the acceptable safety outcomes among vaccine recipients, supports advancement of mRNA-1273 into a large phase 3 clinical trial.”

The phase 3 trial will evaluate the effectiveness of mRNA-1273 for the prevention of COVID-19, compared to no vaccine.

The mRNA-1273 vaccine uses genetic material (mRNA) encoding the SARS-COV-2 spike protein — the protein that protrudes crown-like from the virus surface, giving coronaviruses their name. The spike protein binds to receptors on human cells and enables virus entry. It is required for infection and is the target of many candidate SARS-CoV-2 vaccines.

The idea of the mRNA vaccine is for a person’s cells to use the mRNA instructions to produce spike protein and stimulate an immune response against it. Then, if the vaccinated person is exposed to SARS-CoV-2, their immune system should recognize and neutralize it to prevent infection.

If the mRNA vaccine technology is successful, it might become a routine way to quickly develop vaccines for any emerging viral threat.

The concept and design of the spike protein encoded in the Moderna vaccine was developed by Barney Graham, MD, PhD, a former Vanderbilt faculty member who is now deputy director of the NIAID Vaccine Research Center.

In addition to Denison and Chappell, team members participating in the studies of mRNA-1273 include Laura Stevens, MS, Andrea Pruijssers, PhD, Tia Hughes, MS, and Xiaotao Lu, MS. The studies at VUMC are supported by the NIAID (grant AI148684), the Vanderbilt Institute for Clinical and Translational Research directed by Gordon Bernard, MD (NIH grant TR002243) and the Dolly Parton COVID-19 Research Fund.

— by Leigh MacMillan

Hope – Summer/Fall 2020