An investigational vaccine designed to protect against COVID-19 was generally well tolerated and prompted neutralising activity in healthy adults, according to interim results. The lead author of the study, Dr Lisa A Jackson, a senior investigator at Kaiser Permanente Washington Health Research Institute in Seattle. "The world urgently needs vaccines to protect against COVID-19,” Jackson said. “We are glad to be able to contribute to these efforts by initiating the first clinical trial of a COVID-19 vaccine, which was developed, produced, and put into a first-in-human clinical trial in record time.”
The ongoing phase 1 trial is supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The experimental vaccine is being co-developed by researchers at NIAID and at Moderna Inc of Cambridge, Massachusetts. Manufactured by Moderna, mRNA-1273 is designed to induce neutralising activity to block the virus from binding to and entering human cells.
The first study vaccination was administered on 16 March at Kaiser Permanente Washington Health Research Institute. The interim report details the findings from the first 45 participants ages 18 to 55 years enrolled at the study sites in Seattle and Emory University in Atlanta through 57 days after their first vaccination. Three groups of 15 volunteers received 2 intramuscular injections, 28 days apart, of either 25, 100, or 250 micrograms of the investigational vaccine.
In April, the trial was expanded to enrol adults older than 55 years; it now has 120 participants. However, the newly published results cover the 18- to 55-year age group only.
Regarding safety, no serious adverse events were reported. More than half of the participants reported symptoms including fatigue, headache, chills, muscle aches, or pain at the injection site. Symptoms were more common following the second vaccination and in those who received the highest vaccine dose. Data on side effects and immune responses at various vaccine dosages informed the doses used or planned for use in the phase 2 and 3 clinical trials of the investigational vaccine.
The interim analysis reports on the levels of vaccine-induced neutralising activity – through days 43 to 57 – and the second injection. Two doses of vaccine prompted high levels of neutralising activity that were above the average values seen in convalescent serum obtained from people with confirmed cases of COVID-19 disease.
Abstract
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.
Authors
Lisa A Jackson, 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, II, 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, John H Beigel
[link url="https://www.kpwashingtonresearch.org/news-and-events/recent-news/news-2020/covid-19-vaccine-well-tolerated-generates-immune-response"]Kaiser Permanente Washington Health Research Institute material[/link]
[link url="https://www.nejm.org/doi/full/10.1056/NEJMoa2022483"]NEJM abstract[/link]