15.07.2020

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

Therapeutic InfectiologyVirologyImmunity
Jackson LA et al
NEJM

Main result

After the first vaccination, antibody responses were higher with higher dose, i.e. 250 μg. At day 29, enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT] is 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. At day 57, GMT is 299,751, 782,719, and 1,192,154, respectively for the three dose groups.

Serum-neutralizing activity was detected by two methods : PsVNA responses were identified in serum samples from all participants after the second vaccination and PRNT assay with a titre reducing infectivity by 80% (PNRT80) appears at day 43 in all patients.

Binding antibody IgG geometric mean titers (GMTs) to S-2P increased rapidly after the first vaccination, with seroconversion in all participants by day 15, in a dose-dependent manner to the first and second vaccinations. 

The main side effects reported are mild to moderate in the majority of patients: fatigue, chills, headache, myalgia, and pain at the injection site. 5 participants (33%) in the 25 μg group, 10 (67%) in the 100 μg group, and 8 (53%) in the 250 μg group.

Systemic adverse events were most frequently seen after the second vaccination in 7 of 13 participants (54%) in the 25 μg group, 15 (100%) in the 100 μg group, 14 (100%) in the 250 μg group.

More serious side effects are reported with the highest dose, i.e. 250 μg and occur in only 3 patients (21%).

Takeaways

The mRNA-1273 vaccine is fairly well tolerated. Of the three doses evaluated, the 100-μg dose elicits high neutralization responses and Th1-skewed CD4 T cell responses. No serious side effects requiring cessation of vaccine development have been reported. The vaccine is moving into Phase II to evaluate the 50 and 100 μg doses and will soon move into Phase III with the 100 μg dose. Patients in the study are being followed for 57 days. Patients will be followed up one year later to confirm the persistence of cellular immunity.

Strength of evidence Moderate

The report results are only preliminary, as the 250 μg dose data for PRNT assay are missing of the three doses studied (25 μg, 100 μg and 250 μg).
The 45 patients are healthy adult volunteers, 18 to 55 years of age, not representative of the extreme age groups (young and elderly subjects).
The black population is under-represented only in the 100 μg group (2 patients, i.e. 13%).
3 patients did not strictly follow the protocol.

Objectives

Accelerated development of the Moderna mRNA-1273 vaccine in Phase I: presentation of preliminary results on its ability to induce an immune response against the SARS-CoV-2 infection and investigation of the first side effects, tolerance during its use in humans and the minimum effective dose.

Method

Phase 1, dose-escalation, open-label vaccine trial over the period from 16 March 2020 to 14 April 2020 including 45 healthy adults, 18 to 55 years of age, who received two intramuscular 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. Trial available at clinical.trials.gov: NCT04283461.
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