Curated Papers > High-impact authoritative literature on "mRNA vaccines"

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.

Literature Information

DOI	10.1056/NEJMoa2035389
PMID	33378609
Journal	The New England journal of medicine
Impact Factor	78.5
JCR Quartile	Q1
Publication Year	2021
Times Cited	5937
Keywords	mRNA-1273 vaccine, SARS-CoV-2, vaccine efficacy, safety, clinical trial
Literature Type	Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural
ISSN	0028-4793
Pages	403-416
Issue	384(5)
Authors	Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John McGettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks

TL;DR

The phase 3 trial of the mRNA-1273 vaccine demonstrated a 94.1% efficacy in preventing symptomatic Covid-19 among high-risk individuals, with severe disease occurring only in the placebo group. The findings underscore the vaccine's potential as a crucial tool in combating the pandemic, while revealing minimal safety concerns beyond mild, transient reactions.

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mRNA-1273 vaccine · SARS-CoV-2 · vaccine efficacy · safety · clinical trial

Abstract

BACKGROUND Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.

RESULTS The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.

CONCLUSIONS The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

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Primary Questions Addressed

1. What are the long-term effects of the mRNA-1273 vaccine on different age groups, particularly those over 65?
2. How does the efficacy of the mRNA-1273 vaccine compare to other Covid-19 vaccines in high-risk populations?
3. What factors might influence the observed reactogenicity in individuals receiving the mRNA-1273 vaccine?
4. Are there specific populations or demographics that showed different efficacy rates in the mRNA-1273 trial?
5. What are the implications of the trial results for booster vaccinations with the mRNA-1273 vaccine?

Key Findings

Research Background and Objective

The emergence of SARS-CoV-2 in December 2019 led to a global pandemic, highlighting the urgent need for effective vaccines to prevent COVID-19. The mRNA-1273 vaccine, developed by Moderna, encodes the full-length spike protein of SARS-CoV-2 and is designed to elicit an immune response. This study aimed to evaluate the efficacy and safety of the mRNA-1273 vaccine in preventing symptomatic COVID-19 in high-risk populations.

Main Methods/Materials/Experimental Design

This phase 3 randomized, observer-blinded, placebo-controlled trial involved 30,420 participants at 99 centers across the United States. Participants aged 18 years or older, at high risk for SARS-CoV-2 infection, were randomly assigned in a 1:1 ratio to receive two intramuscular injections of either mRNA-1273 (100 μg) or a placebo, 28 days apart. The primary endpoint was the prevention of symptomatic COVID-19 illness occurring at least 14 days after the second dose.

Key Results and Findings

• Efficacy: The vaccine demonstrated 94.1% efficacy (95% CI, 89.3 to 96.8; P<0.001) in preventing symptomatic COVID-19. In the placebo group, 185 cases were confirmed, while only 11 cases occurred in the mRNA-1273 group.
• Safety: Common adverse events included local reactions (pain, erythema) and systemic reactions (fatigue, headache). Serious adverse events were rare and similar between groups. Notably, all severe COVID-19 cases occurred in the placebo group, indicating a potential protective effect of the vaccine against severe illness.
• Demographics: The trial population included a diverse demographic, with 24.8% of participants aged 65 or older and 20.5% identifying as Hispanic or Latino.

Main Conclusion/Significance/Innovation

The mRNA-1273 vaccine exhibits high efficacy in preventing symptomatic COVID-19, particularly severe cases, and has a favorable safety profile. The findings support the use of mRNA vaccines as a crucial tool in combating the COVID-19 pandemic. This trial demonstrates the rapid development and assessment capabilities for vaccines during a global health crisis.

Research Limitations and Future Directions

• Short Follow-Up: The duration of safety and efficacy follow-up was limited to a median of 64 days post-vaccination. Ongoing studies will provide longer-term data.
• Correlate of Protection: There is currently no identified correlate of protection, which is essential for future studies.
• Population Gaps: The trial did not include pregnant women or children, indicating a need for further evaluation in these groups.

Future studies should focus on long-term efficacy, monitoring for potential rare adverse events, and evaluating vaccine effectiveness against emerging variants of SARS-CoV-2. Additionally, ongoing research will aim to clarify the vaccine's impact on asymptomatic infections and transmission dynamics.

References

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Literatures Citing This Work

1. Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates. - Linling He;Xiaohe Lin;Ying Wang;Ciril Abraham;Cindy Sou;Timothy Ngo;Yi Zhang;Ian A Wilson;Jiang Zhu - bioRxiv : the preprint server for biology (2021)
2. Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada. - Thomas N Vilches;Shokoofeh Nourbakhsh;Kevin Zhang;Lyndon Juden-Kelly;Lauren E Cipriano;Joanne M Langley;Pratha Sah;Alison P Galvani;Seyed M Moghadas - medRxiv : the preprint server for health sciences (2021)
3. A New Vaccine to Battle Covid-19. - Barton F Haynes - The New England journal of medicine (2021)
4. Search for better COVID vaccines confounded by existing rollouts. - Elie Dolgin - Nature (2021)
5. Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques. - Neeltje van Doremalen;Jyothi N Purushotham;Jonathan E Schulz;Myndi G Holbrook;Trenton Bushmaker;Aaron Carmody;Julia R Port;Claude K Yinda;Atsushi Okumura;Greg Saturday;Fatima Amanat;Florian Krammer;Patrick W Hanley;Brian J Smith;Jamie Lovaglio;Sarah L Anzick;Kent Barbian;Craig Martens;Sarah Gilbert;Teresa Lambe;Vincent J Munster - bioRxiv : the preprint server for biology (2021)
6. The art of prevention: COVID-19 vaccine preparedness for the dermatologist. - Shauna M Rice;Sarah D Ferree;Natasha Atanaskova Mesinkovska;Arianne Shadi Kourosh - International journal of women's dermatology (2021)
7. The Intersection of Photopheresis and COVID-19 Vaccination. - Garrett S Booth;Bipin N Savani - Transplantation and cellular therapy (2021)
8. [STIKO vaccination recommendations : Vaccination of immunodeficient patients and vaccination against COVID-19]. - Christian Bogdan - Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete (2021)
9. Doctor-Should I get the COVID-19 vaccine? Infection and immunization in individuals with neuromuscular disorders. - Sasha A Živković;Gregory Gruener;Pushpa Narayanaswami; - Muscle & nerve (2021)
10. SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for COVID-19. - Ilaria Vicenti;Maurizio Zazzi;Francesco Saladini - Expert opinion on therapeutic patents (2021)

... (5927 more literatures)

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