Homologous and Heterologous Covid-19 Booster Vaccinations.
2019-nCoV Vaccine mRNA-1273
/ immunology
Ad26COVS1
/ immunology
Adult
Aged
Aged, 80 and over
Antibodies, Neutralizing
/ blood
Antibodies, Viral
/ blood
BNT162 Vaccine
/ immunology
COVID-19 Vaccines
/ adverse effects
Female
Humans
Immunization, Secondary
/ adverse effects
Immunogenicity, Vaccine
Injections, Intramuscular
/ adverse effects
Male
Middle Aged
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ immunology
T-Lymphocytes
/ immunology
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 03 2022
17 03 2022
Historique:
pubmed:
27
1
2022
medline:
23
3
2022
entrez:
26
1
2022
Statut:
ppublish
Résumé
Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×10 Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).
Sections du résumé
BACKGROUND
Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients.
METHODS
In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×10
RESULTS
Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients.
CONCLUSIONS
Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).
Identifiants
pubmed: 35081293
doi: 10.1056/NEJMoa2116414
pmc: PMC8820244
doi:
Substances chimiques
Ad26COVS1
JT2NS6183B
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
BNT162 Vaccine
N38TVC63NU
Banques de données
ClinicalTrials.gov
['NCT04889209']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1046-1057Subventions
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148450
Organisme : NIAID NIH HHS
ID : UM1 AI148372
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148574
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148575
Organisme : NIAID NIH HHS
ID : UM1 AI148452
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00050
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148450
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148576
Organisme : NIAID NIH HHS
ID : UM1 AI148689
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148575
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148576
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI074492
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148452
Organisme : NIAID NIH HHS
ID : UM1 AI148573
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148373
Organisme : NIAID NIH HHS
ID : UM1 AI148373
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148689
Organisme : NIAID NIH HHS
ID : UM1 AI148684
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148684
Organisme : NIAID NIH HHS
ID : UM1 AI148574
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148573
Organisme : National Institute of Allergy and Infectious Diseases
ID : UM1AI148372
Investigateurs
Robert L Atmar
(RL)
Hana El Sahly
(H)
Jennifer A Whitaker
(JA)
Wendy A Keitel
(WA)
Kirsten E Lyke
(KE)
Meagan Deming
(M)
Jennifer S Husson
(JS)
Angie Price
(A)
Lisa A Jackson
(LA)
Angela Branche
(A)
David Dobryzynski
(D)
Ann R Falsey
(AR)
Ian Shannon
(I)
Srilatha Edupuganti
(S)
Paulina A Rebolledo
(PA)
Nadine Rouphael
(N)
Christina Rostad
(C)
Andres F Camacho-Gonzalez
(AF)
Satoshi Kamidani
(S)
Judith Martin
(J)
Kumaravel Rajakumar
(K)
Gysella B Muniz
(GB)
Sonika Bhatnagar
(S)
Christine Johnston
(C)
Tara M Babu
(TM)
Anna Wald
(A)
Richard E Rupp
(RE)
Megan Berman
(M)
Laura Porterfield
(L)
Amber Stanford
(A)
Mark J Mulligan
(MJ)
Angelica Cifuentes Kottkamp
(A)
Jennifer Lee Dong
(JL)
Martín Bäcker
(M)
Steven E Carsons
(SE)
Diana Badillo
(D)
Rebecca Brady
(R)
Robert W Frenck
(RW)
Susan Parker
(S)
Michelle Dickey
(M)
Rhea N Coler
(RN)
Sasha E Larsen
(SE)
Christine M Posavad
(CM)
John Hural
(J)
Kathleen M Neuzil
(KM)
David Stephens
(D)
Elizabeth R Brown
(ER)
Clara Dominguez Islas
(C)
Jillian Zemanek
(J)
Daniel Szydlo
(D)
Rahul Paul Choudhury
(RP)
Sonja Crandon
(S)
Marina Lee
(M)
Seema Nayak
(S)
Paul C Roberts
(PC)
John Beigel
(J)
Janet I Archer
(JI)
Adrian McDermott
(A)
Sarah O'Connell
(S)
Bob Lin
(B)
David Montefiori
(D)
Amanda Eaton
(A)
Mehul S Suthar
(MS)
Lilin Lai
(L)
M Juliana McElrath
(MJ)
Kristen W Cohen
(KW)
Stephen De Rosa
(S)
Mary Healy
(M)
Christine Akamine
(C)
Pedro A Piedra
(PA)
Chanei Henry
(C)
Brandie Phillips
(B)
Chianti Wade-Bowers
(C)
Connie Rangel
(C)
Logan Lee
(L)
Julia Guardado
(J)
Angelica Diaz
(A)
Lisreina Toro
(L)
Tina Sierra
(T)
Janet Brown
(J)
Cathy Faw
(C)
Yvette Rugeley
(Y)
Yolanda Rayford
(Y)
Kayla Burrell
(K)
Jesus Banay
(J)
Tykel Eddy
(T)
Marinna Matta
(M)
Kathy Bosworth
(K)
Meagan E Deming
(ME)
Joel Chua
(J)
Karen Kotloff
(K)
Myounghee Lee
(M)
Lisa Anderson
(L)
Amy Nelson
(A)
Salma Sharaf
(S)
Young Chae Jessica Yoo
(YCJ)
Lisa Langer
(L)
Brenda Dorsey
(B)
Alyson Kwon
(A)
Sophie Harper
(S)
Paula Bernal
(P)
Eric Goldstein
(E)
Jeffrey Floyd
(J)
Regina Harley
(R)
Marcelo Sztein
(M)
Ming Bell
(M)
Leslie Howe
(L)
Erika Stiles
(E)
Andrew Chi
(A)
Phuong Tran Nguyen
(PT)
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(Y)
Christine Aggabao
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Jeannie Murray
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Lee Barr
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