Skip to main content

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

Our take —

The mRNA-1273 COVID-19 vaccine from Moderna shows promise as it has been proven overall safe in phase 1 clinical trials, as well as immunogenic. The medium dose of 100ug elicited high neutralization responses, as well as Th1 CD4 T-cell responses, and is moving on to a phase 2 trial. True correlates of protection against SARS-CoV-2 have not yet been determined, so it is difficult to say for certain whether this vaccine will provide protection in the long term. Participants from this trial will be followed for one year, so we are not yet able to comment on the resilience of the immune response elicited from the vaccine.

Study design

Randomized Controlled Trial

Study population and setting

This study was a phase 1 clinical trial including 45 healthy adults between the ages of 18 and 55 years old divided evenly into three groups receiving low, medium, and high doses of Moderna’s mRNA-1273 vaccine in two injections 28 days apart. This analysis includes results through follow-up on day 57.

Summary of Main Findings

Following the first vaccination, antibody responses increased in a dose dependent fashion, with seroconversion in all participants by day 15. Antibody titers increased dose-dependently again after the second dose vaccination. Neutralizing antibodies were detected in all participants after the second dose via two methods. This supports the need for a two-dose vaccination schedule. Neutralizing antibodies in trial participants reached similar levels to those in convalescent serum samples. The most common adverse events included fatigue, chills, headache, myalgia, and pain at injection site, with a greater incidence following the second vaccine dose. All 15 participants in the medium dose group and 14/15 in the high dose group reported solicited systemic adverse events following the second dose. The highest number of overall adverse events was in the high dose group, and 3/15 in this group reported severe adverse events, including fever.

Study Strengths

This study was an example of deployment of a vaccine for human clinical trials in record time, taking only two months to accomplish a task that normally takes years to complete. The safety profile of this vaccine is similar to that of other previously published Moderna influenza mRNA vaccines. The mRNA-1273 vaccine proved to be immunogenic in all participants, with all showing binding and neutralizing antibody responses. These responses were similar to antibody levels detected in convalescent serum specimens.

Limitations

This trial included a small number of participants, which is consistent with phase 1 study design. However, 89% of participants were white. More diversity is needed in the phase 2 cohort, especially since SARS-CoV-2 has disproportionately affected minority populations in the US. Additionally, most patients were around 30 years of age, while the older population is a group that needs the most protection from the virus. There were a few instances of severe adverse events reported in the high dose group. Additionally, no detection of a T-cell response was mentioned for the high dose group.

Value added

First report of results from the mRNA-1273 vaccine’s phase 1 trial, with promising findings warranting proceeding to phase 2 trials.

This review was posted on: 18 July 2020