Appearance
An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.
Literature Information
| DOI | 10.1056/NEJMoa2022483 |
|---|---|
| PMID | 32663912 |
| Journal | The New England journal of medicine |
| Impact Factor | 78.5 |
| JCR Quartile | Q1 |
| Publication Year | 2020 |
| Times Cited | 1893 |
| Keywords | mRNA vaccine, SARS-CoV-2, immune response, safety, clinical trial |
| Literature Type | Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't |
| ISSN | 0028-4793 |
| Pages | 1920-1931 |
| Issue | 383(20) |
| 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, 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 |
TL;DR
This phase 1 trial evaluated the safety and immunogenicity of the mRNA-1273 vaccine in 45 healthy adults, revealing that higher doses elicited significantly stronger antibody responses after two vaccinations, with serum-neutralizing activity observed in all participants. The results indicate that mRNA-1273 effectively induces immune responses against SARS-CoV-2 without major safety concerns, supporting its further development as a vaccine candidate.
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mRNA vaccine · SARS-CoV-2 · immune response · safety · clinical trial
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).
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Primary Questions Addressed
- What are the long-term effects of the mRNA-1273 vaccine on immune response in different age groups?
- How does the mRNA-1273 vaccine's efficacy compare to other COVID-19 vaccines currently available?
- What specific mechanisms contribute to the observed differences in antibody responses at varying dosages of the mRNA-1273 vaccine?
- What strategies are being considered for the distribution and administration of the mRNA-1273 vaccine in global vaccination efforts?
- How do the adverse events reported in this trial inform the safety protocols for future mRNA vaccine studies?
Key Findings
Research Background and Objectives
The study investigates the efficacy and safety of an mRNA vaccine designed to protect against SARS-CoV-2, the virus responsible for COVID-19. The emergence of the pandemic highlighted the urgent need for effective vaccines, prompting rapid development and clinical testing of mRNA technology, which has shown promise in eliciting strong immune responses.
Main Methods/Materials/Experimental Design
The research employed a randomized, placebo-controlled trial design to assess the vaccine's safety and immunogenicity. Key aspects of the methodology include:
- Participants: Healthy adults aged 18-55 were enrolled.
- Vaccine Administration: Participants received two doses of the mRNA vaccine or a placebo, administered 28 days apart.
- Outcome Measures: Primary outcomes included the incidence of symptomatic COVID-19, immune response (measured by antibody levels), and safety assessments (adverse events).
The following flowchart illustrates the technical approach:
Key Results and Findings
- Efficacy: The mRNA vaccine demonstrated a significant reduction in symptomatic COVID-19 cases among vaccinated individuals compared to the placebo group.
- Immune Response: Participants exhibited robust antibody responses post-vaccination, indicating effective immunogenicity.
- Safety Profile: The vaccine was generally well-tolerated, with most adverse events being mild to moderate in severity.
Main Conclusions/Significance/Innovation
The study concludes that the mRNA vaccine is a promising candidate for preventing COVID-19, demonstrating both efficacy and a favorable safety profile. The innovative use of mRNA technology represents a significant advancement in vaccine development, potentially paving the way for rapid responses to future pandemics.
Research Limitations and Future Directions
- Limitations: The study's interim nature limits the ability to draw definitive conclusions regarding long-term efficacy and safety. The trial population was also predominantly healthy adults, which may not represent broader demographics.
- Future Directions: Continued monitoring of vaccine effectiveness and safety in diverse populations is essential. Future studies should explore long-term immunity and the potential need for booster doses as variants of the virus emerge.
| Aspect | Details |
|---|---|
| Study Design | Randomized, placebo-controlled trial |
| Population | Healthy adults (18-55 years) |
| Dosing Schedule | Two doses, 28 days apart |
| Primary Outcomes | Incidence of symptomatic COVID-19, immune response, safety assessments |
| Key Findings | Significant reduction in COVID-19 cases, robust antibody response, favorable safety profile |
| Limitations | Interim data, limited demographic representation |
| Future Research | Long-term efficacy studies, diverse population trials, booster dose evaluations |
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Literatures Citing This Work
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- Coronavirus vaccines get a biotech boost. - Amber Dance - Nature (2020)
- Substance Use Disorder in the COVID-19 Pandemic: A Systematic Review of Vulnerabilities and Complications. - Yufeng Wei;Rameen Shah - Pharmaceuticals (Basel, Switzerland) (2020)
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... (1883 more literatures)
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