An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.
2019-nCoV Vaccine mRNA-1273
Adult
Antibodies, Neutralizing
/ blood
Antibodies, Viral
/ blood
Antibody Formation
Betacoronavirus
COVID-19
COVID-19 Vaccines
Coronavirus Infections
/ prevention & control
Female
Humans
Immunization, Secondary
Male
Pandemics
/ prevention & control
Pneumonia, Viral
/ prevention & control
RNA, Messenger
/ immunology
SARS-CoV-2
Spike Glycoprotein, Coronavirus
/ immunology
T-Lymphocytes
/ immunology
Viral Vaccines
/ adverse effects
Young Adult
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
12 11 2020
12 11 2020
Historique:
pubmed:
15
7
2020
medline:
18
11
2020
entrez:
15
7
2020
Statut:
ppublish
Résumé
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. 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. 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. 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).
Sections du résumé
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).
Identifiants
pubmed: 32663912
doi: 10.1056/NEJMoa2022483
pmc: PMC7377258
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
RNA, Messenger
0
Spike Glycoprotein, Coronavirus
0
Viral Vaccines
0
spike protein, SARS-CoV-2
0
2019-nCoV Vaccine mRNA-1273
EPK39PL4R4
Banques de données
ClinicalTrials.gov
['NCT04283461']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1920-1931Subventions
Organisme : NIAID NIH HHS
ID : R38 AI140299
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148576
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148373
Pays : International
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148684
Pays : International
Organisme : NIAID NIH HHS
ID : UM1 AI148373
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148684
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201500002C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002378
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148576
Pays : International
Investigateurs
Jae Arega
(J)
John H Beigel
(JH)
Wendy Buchanan
(W)
Mohammed Elsafy
(M)
Ranjodh Gill
(R)
Binh Hoang
(B)
Sonnie Kim
(S)
Hyung Koo
(H)
Marina Lee
(M)
Catherine Luke
(C)
Mamodikoe Makhene
(M)
Jorge Mejia-Galvis
(J)
Seema Nayak
(S)
Rhonda Pikaart-Tautges
(R)
Paul C Roberts
(PC)
Elisa Sindall
(E)
Jim Albert
(J)
Kaitlyn Cross
(K)
Mat Makowski
(M)
Evan J Anderson
(EJ)
Amer Bechnak
(A)
Mary Bower
(M)
Matthew Collins
(M)
Ana Drobeniuc
(A)
Srilatha Edupuganti
(S)
Theda Gibson
(T)
Brandi Johnson
(B)
Carol Kao
(C)
Colleen Kelley
(C)
Hollie Macenczak
(H)
Michele Paine McCullough
(M)
Amanda Panepento
(A)
Etza Peters
(E)
Varun Phadke
(V)
Christina Rostad
(C)
Nadine Rouphael
(N)
Erin Scherer
(E)
Amy Sherman
(A)
Cynthia Whitney
(C)
Juton Winston
(J)
Inci Yildirim
(I)
Barbara A Carste
(BA)
Maya B Dunstan
(MB)
Lisa A Jackson
(LA)
Hamilton Bennett
(H)
Nedim Emil Altaras
(NE)
Andrea Carfi
(A)
Marjorie Hurley
(M)
Brett Leav
(B)
Rolando Pajon
(R)
Wellington Sun
(W)
Tal Zaks
(T)
Rhea N Coler
(RN)
Sasha E Larsen
(SE)
Kathleen M Neuzil
(KM)
Kevin Carlton
(K)
Kizzmekia S Corbett
(KS)
Nicole A Doria-Rose
(NA)
Britta Flach
(B)
Martin Gaudinski
(M)
Ingelise Gordon
(I)
Barney S Graham
(BS)
Julie E Ledgerwood
(JE)
Bob C Lin
(BC)
Mark K Louder
(MK)
John R Mascola
(JR)
Adrian B McDermott
(AB)
Kaitlyn M Morabito
(KM)
Laura Novik
(L)
Sijy O'Dell
(S)
Marcelino Padilla
(M)
Stephen D Schmidt
(SD)
Phillip A Swanson
(PA)
Lingshu Wang
(L)
Alicia Widge
(A)
James D Chappell
(JD)
Mark R Denison
(MR)
Tia Hughes
(T)
Andrea J Pruijssers
(AJ)
Laura J Stevens
(LJ)
Xiaotao Lu
(X)
Cassandra Karcs
(C)
Pratap Kunwar
(P)
Ava Manokian
(A)
Eli Sendra
(E)
Alexis Ahonen
(A)
Ghina Alaaeddine
(G)
Larry Anderson
(L)
Teresa Ball
(T)
Richard L Bearden
(RL)
Sydney Biccum
(S)
Laurel Bristow
(L)
Andreas Camacho-Gonzalez
(A)
Xuemin Chen
(X)
Laura Clegg
(L)
Francine Dyer
(F)
Felicia Glover
(F)
Lisa Harewood
(L)
Laila Hussaini
(L)
Hui-Mien Hsiao
(HM)
Satoshi Kamidani
(S)
Peggy Kettle
(P)
Wensheng Li
(W)
Lisa Macoy
(L)
Amy Muchinsky
(A)
G Osinski
(G)
Brittany Robinson
(B)
Susan Rogers
(S)
Youssef Saklawi
(Y)
Amber Samuel
(A)
Oliver Smith
(O)
Kathleen Stephens
(K)
Mehgan Teherani
(M)
Ashley Tippett
(A)
Sean Todd
(S)
Jessica Traenkner
(J)
Dongli Wang
(D)
Terra Jean Winter
(TJ)
Jianguo Xu
(J)
Yongxian Xu
(Y)
Kathryn Zaks
(K)
Lee Barr
(L)
Joyce Benoit
(J)
Heather Beseler
(H)
Rachael Burganowski
(R)
Barbara Carste
(B)
Joe Choe
(J)
John Dunn
(J)
Maya Dunstan
(M)
Roxanne Erolin
(R)
Jana Ffitch
(J)
Colin Fields
(C)
Erika Kiniry
(E)
De Vona Lang
(V)
Susan Lasicka
(S)
Stella Lee
(S)
Matthew Nguyen
(M)
Jennifer Nielsen
(J)
Hallie Phillips
(H)
Stephanie Pimienta
(S)
David Skatula
(D)
Janice Suyehira
(J)
Karen Wilkinson
(K)
Michael Witte
(M)
Rodrigo Laureano
(R)
Tiffany Pecor
(T)
Brian Granger
(B)
Valerie A Reese
(VA)
Evan Cross
(E)
Susan L Baldwin
(SL)
James M Ferrenberg
(JM)
Bryan Berube
(B)
Seyhan Boyoglu-Barnum
(S)
Rebecca A Gillespie
(RA)
Eun Sung Yang
(ES)
Yi Zhang
(Y)
Helen Chu
(H)
David Ho
(D)
Gordon Bernard
(G)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 Massachusetts Medical Society.
Références
Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7348-E7357
pubmed: 28807998
Nature. 2020 Oct;586(7830):567-571
pubmed: 32756549
Cell Rep. 2019 Sep 24;28(13):3395-3405.e6
pubmed: 31553909
Nature. 2016 Mar 3;531(7592):118-21
pubmed: 26935699
N Engl J Med. 2007 Sep 13;357(11):1162-3
pubmed: 17855683
Vaccine. 2023 Aug 31;41(38):5622-5629
pubmed: 37532612
Nature. 2021 Feb;590(7844):E24
pubmed: 33469217
Emerg Infect Dis. 2007 Oct;13(10):1562-4
pubmed: 18258008
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Viruses. 2012 Jun;4(6):1011-33
pubmed: 22816037
Vaccine. 2019 May 31;37(25):3326-3334
pubmed: 31079849
Cell. 2020 May 28;181(5):1004-1015.e15
pubmed: 32375025
Lancet. 2020 Jun 13;395(10240):1845-1854
pubmed: 32450106
Nature. 2020 Apr;580(7805):576-577
pubmed: 32346146
Science. 2019 Aug 2;365(6452):505-509
pubmed: 31371616
J Exp Med. 2018 Jun 4;215(6):1571-1588
pubmed: 29739835
PLoS One. 2013;8(3):e57755
pubmed: 23526951
Nat Commun. 2020 May 20;11(1):2601
pubmed: 32433465
Clin Infect Dis. 2020 Dec 17;71(10):2688-2694
pubmed: 32497196
J Clin Med. 2020 Apr 24;9(4):
pubmed: 32344679
Viral Immunol. 2018 Mar;31(2):195-203
pubmed: 29336703
PLoS One. 2015 Jun 24;10(6):e0131531
pubmed: 26107625
Science. 2020 May 29;368(6494):945-946
pubmed: 32385100
Emerg Infect Dis. 2017 Jul;23(7):1079-1084
pubmed: 28585916
Emerg Infect Dis. 2020 Jul;26(7):1478-1488
pubmed: 32267220
Science. 2020 Aug 14;369(6505):806-811
pubmed: 32434945
Science. 2020 Aug 14;369(6505):812-817
pubmed: 32434946
Annu Rev Med. 2019 Jan 27;70:91-104
pubmed: 30691364
Sci Rep. 2018 Oct 24;8(1):15701
pubmed: 30356097