Review of NEJM An mRNA Vaccine against SARS-CoV-2 — Preliminary Report, Jackson 2020
In the article An mRNA Vaccine against SARS-CoV-2 — Preliminary Report published, July 14, 2020, by Jackson and Colleagues, a Phase 1, dose-escalation, open-label trial study, investigating the question is the mRNA-1273 vaccination safe and immunogenic in healthy adults? 45 patients were enrolled, individuals who were between 18 and 55 years old and healthy. Patients in the sample were from two medical facilities, in Seattle, Washington and Atlanta, Georgia, both in United States of America. The study enrolled patients and administered the first dose of vaccination on April 14, 2020, with specimen collection to extend until day 57 of trial.
Results were measured by enzyme linked immunosorbent assay and plaque-reduction neutralization and testing assay titres to binding antibodies against S-2P isolated receptor binding domains on the S1 subunit. Vaccine induced neutralizizing activity was measured by the pseudotyped lentivirus reporter single round of infection neuutralization assay (PsVNA) and live wild type SARSCOV2 plaque reduction neutralization test assay, collected on days 1, 15, 29, 36, 43 and 57 (not summarized in this review). Intracellular cytokine staining was performed to identify T Helper type response profiles (not summarized in this review). See full article for further methodological information.
Outcomes of the study revealed safety data obtained revealed adverse events in 23 out of 45 patients after the first vaccination round, deemed to be mild or moderate in grading. Adverse events were noted in 36 out of 45 patients in the second vaccination round. Severe adverse events were reported in 3 out of 45 patients. Patients with severe adverse reactions were only 21% of patients recieving the 250 ug (high dose) vaccine. The severe adverse reactions that were experienced fell into the symptom classes of: systemic, fatigue, chills, myalgia, headache, fever, nausea, and erythema. Higher antibody responses with higher doses based on post vaccination day 57 enzyme linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 299,751 in the 25 ug group, 782,719 in the 100 ug group, and 1,192,154 in the 250 ug group. 21% of trial participants in the 250 ug dose vaccine group reported one or more serious adverse events after the third dose. Plaque reduction neutralization testing assay was also done, please see full article for results.
There were some limitations in the study of which none were explicitly identified by the authors. As this is a Phase 1 Vaccination Trial, the purpose is to gauge safety in a small pool of research consented trial patients. Therefore although it is a small sample, the question of the study is not effectiveness but safety. When it comes to safety, severe grade symptoms were noted in patients recieving the 250 ug dose more frequently than the patients recieving the 100 ug dose. The sample population tested for safety was disproportionately white, 89% or 40 out of 45 patient, yet COVID-19 afflicted communities of color with serious illness and death. The safety data may not be broadly applicable to the United States population as a result, however larger Phase 2 trials or preferred repeat Phase 1 trials should be optioned for more specified safety parameters for intermediate and high dose vaccination.
On an ending note, the authors mentioned that the immunologic characteristics of the mRNA-1273 vaccine in this study support later phase trial advancement. They mentioned that a phase 2 trial of mRNA-1273 in 600 healthy adults is being evaluated in the 100 ug and 50 ug dosing and a larger phase 3 efficacy trial of the 100 ug vaccine is anticipated during summer of 2020.
Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, McCullough MP, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott A, Flach B, Doria-Rose NA, Corbett KS, Morabito KM, O'Dell S, Schmidt SD, Swanson PA 2nd, Padilla M, Mascola JR, Neuzil KM, Bennett H, Sun W, Peters E, Makowski M, Albert J, Cross K, Buchanan W, Pikaart-Tautges R, Ledgerwood JE, Graham BS, Beigel JH; mRNA-1273 Study Group. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020 Nov 12;383(20):1920-1931. doi: 10.1056/NEJMoa2022483. Epub 2020 Jul 14. PMID: 32663912; PMCID: PMC7377258.
Review completed July 15, 2020
