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

By L. Jackson, E. Anderson, N. Rouphael, P. Roberts, M. Makhene, R. Coler, M. McCullough, J. Chappell, M. Denison, Laura J. Stevens and 23 more. 2020

2,864 citations recorded by the source corpus.

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. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).

Subfields: Infectious Diseases, Molecular Biology

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Citations in the corpus

SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development (2020, background): “The results of the mRNA-1273 vaccine phase I clinical trial in 45 healthy adults (18–55 years old) show a strong antibody and cellular immune response in participants and no safety concerns are identified (Jackson et al., 2020).”
Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity (2020, positive): “…on the elicitation of neutralizing antibodies (Amanat and Kram-mer, 2020; Corey et al., 2020; Thanh Le et al., 2020), with additional interest in elicitation of CD4 + or CD8 + T cells (Corbett et al., 2020; Folegatti et al., 2020; Jackson et al., 2020; Mercado et al., 2020; Sahin et al., 2020).”
Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia (2020, methodology): “28,31 In our study, we used a high dose of virus (100 TCID50) and a small amount of serum (50 µL serum and 50 µL of virus), whereas in studies of other vaccines, doses of 58–70 TCID50 and a larger amount of serum were used for analyses.”
Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults (2020, neutral): “Shown are reciprocal end-point binding IgG titers on receptor-binding domain (RBD) enzyme-linked immunosorbent assay (ELISA) (Panel A), along with titers to 614D on the pseudovirus neutralization assay at a 50% inhibitory dilution (ID50) (Panel B), on the focus reduction neutralization test mNeonGre”