Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.
2019-nCoV Vaccine mRNA-1273
Aged
Antibodies, Neutralizing
/ blood
Antibodies, Viral
/ blood
COVID-19
/ immunology
COVID-19 Vaccines
/ administration & dosage
Dose-Response Relationship, Drug
Female
Humans
Male
Middle Aged
Neutralization Tests
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
T-Lymphocytes
/ physiology
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:
17 12 2020
17 12 2020
Historique:
pubmed:
30
9
2020
medline:
29
12
2020
entrez:
29
9
2020
Statut:
ppublish
Résumé
Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti-S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.).
Sections du résumé
BACKGROUND
Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age.
METHODS
We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart.
RESULTS
Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti-S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells.
CONCLUSIONS
In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.).
Identifiants
pubmed: 32991794
doi: 10.1056/NEJMoa2028436
pmc: PMC7556339
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
Spike Glycoprotein, Coronavirus
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
2427-2438Subventions
Organisme : NIAID NIH HHS
ID : R38 AI140299
Pays : United States
Organisme : United States
ID : UM1AI148576
Pays : United States
Organisme : United States
ID : HHSN272201500002C
Pays : United States
Organisme : United States
ID : UM1Al148684-01S1
Pays : United States
Organisme : United States
ID : UM1AI148684
Pays : United States
Organisme : United States
ID : P51 OD011132
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148373
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002378
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201500002C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148576
Pays : United States
Organisme : United States
ID : UM1AI148373
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Organisme : United States
ID : AI149644
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI149644
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148684
Pays : United States
Investigateurs
Jae Arega
(J)
John H Beigel
(JH)
Wendy Buchanan
(W)
Mohammed Elsafy
(M)
Binh Hoang
(B)
Sonnie Kim
(S)
Aparna Kolhekar
(A)
Hyung Koo
(H)
Catherine Luke
(C)
Mamodikoe Makhene
(M)
Seema Nayak
(S)
Rhonda Pikaart-Tautges
(R)
Paul C Roberts
(PC)
Janie Russell
(J)
Elisa Sindall
(E)
Jim Albert
(J)
Kaitlyn Cross
(K)
Mat Makowski
(M)
Evan J Anderson
(EJ)
Amer Bechnak
(A)
Mary Bower
(M)
Andres F Camacho-Gonzalez
(AF)
Matthew Collins
(M)
Ana Drobeniuc
(A)
Venkata Viswanadh Edara
(VV)
Srilatha Edupuganti
(S)
Katharine Floyd
(K)
Theda Gibson
(T)
Cassie M Grimsley Ackerley
(CM)
Brandi Johnson
(B)
Satoshi Kamidani
(S)
Carol Kao
(C)
Colleen Kelley
(C)
Hollie Macenczak
(H)
Michele Paine McCullough
(M)
Etza Peters
(E)
Varun K Phadke
(VK)
Christina A Rostad
(CA)
Nadine Rouphael
(N)
Erin Scherer
(E)
Amy Sherman
(A)
Kathy Stephens
(K)
Mehul S Suthar
(MS)
Mehgan Teherani
(M)
Jessica Traenkner
(J)
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)
Lisa C Lindesmith
(LC)
David R Martinez
(DR)
Jennifer Munt
(J)
Michael Mallory
(M)
Caitlin Edwards
(C)
Ralph S Baric
(RS)
Nina M Berkowitz
(NM)
Kevin Carlton
(K)
Kizzmekia S Corbett
(KS)
Pamela Costner
(P)
Nicole A Doria-Rose
(NA)
Britta Flach
(B)
Martin Gaudinski
(M)
Ingelise Gordon
(I)
Barney S Graham
(BS)
LaSonji Holman
(L)
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)
Amarendra Pegu
(A)
Stephen D Schmidt
(SD)
Phillip A Swanson
(PA)
Lingshu Wang
(L)
Alicia T Widge
(AT)
Eun Sung Yang
(ES)
Yi Zhang
(Y)
James D Chappell
(JD)
Mark R Denison
(MR)
Tia Hughes
(T)
Xiaotao Lu
(X)
Andrea J Pruijssers
(AJ)
Laura J Stevens
(LJ)
Christine M Posavad
(CM)
Michael Gale
(M)
Ranjodh Gill
(R)
Marina Lee
(M)
Jorge Mejia-Galvis
(J)
Cassandra Karcs
(C)
Pratap Kunwar
(P)
Ava Manokian
(A)
Eli Sendra
(E)
Semhal Selamawi
(S)
Alexis Ahonen
(A)
Ghina Alaaeddine
(G)
LaCarles Allen
(L)
Larry Anderson
(L)
Teresa Ball
(T)
Richard L Bearden
(RL)
Sydney Biccum
(S)
Laurel Bristow
(L)
Xuemin Chen
(X)
Laura Clegg
(L)
Francine Dyer
(F)
Felicia Glover
(F)
Lisa Harewood
(L)
Laila Hussaini
(L)
Hui-Mien Hsiao
(HM)
Peggy Kettle
(P)
Wensheng Li
(W)
Cindy Lubbers
(C)
Lisa Macoy
(L)
Amy Muchinsky
(A)
G Osinski
(G)
Amanda Panepento
(A)
Brittany Robinson
(B)
Susan Rogers
(S)
Christina Rostad
(C)
Youssef Saklawi
(Y)
Amber Samuel
(A)
Oliver Smith
(O)
Kathleen Stephens
(K)
Ashley Tippett
(A)
Sean Todd
(S)
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)
Charla Andrews
(C)
Preeti Apte
(P)
Anita Arthur
(A)
Allison Beck
(A)
Seyhan Boyoglu-Barnum
(S)
Eugeania Burch
(E)
Cora Trelles Cartagena
(C)
Joe Casazza
(J)
Emily Coates
(E)
Jennifer Cunningham
(J)
Aba Eshun
(A)
Catina Evans
(C)
Rebecca A Gillespie
(RA)
Carmencita S Graves
(CS)
Mercy Guech
(M)
Cynthia Starr Hendel
(C)
Renunda Hicks
(R)
Kate Houser
(K)
Justine Jones
(J)
Brenda Larkin
(B)
Lam Le
(L)
Lauren Lizewski
(L)
Floreliz Mendoza
(F)
John Misasi
(J)
Patricia Morgan
(P)
Thuy Nguyen
(T)
Mark O'Callahan
(M)
Abidemi Ola
(A)
Karen Parker
(K)
Iris Pittman
(I)
Sarah Plummer
(S)
La'Shawn Requilman
(L)
Ro Rothwell
(R)
Jamie Saunders
(J)
Ellie Seo
(E)
Sandra Sitar
(S)
Stephanie Taylor
(S)
Shinyi Telscher
(S)
Colin Tran
(C)
Olga Trofymenko
(O)
Olga Vasilenko
(O)
Xiaolin Wang
(X)
William Whalen
(W)
Pernell Williams
(P)
Galina Yamshchikov
(G)
Kathy Zephir
(K)
Yi Zhang
(Y)
Helen Chu
(H)
David Ho
(D)
Gordon Bernard
(G)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Massachusetts Medical Society.
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