Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials.
Humans
COVID-19 Vaccines
/ immunology
COVID-19
/ prevention & control
Female
Male
SARS-CoV-2
/ immunology
Adult
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Middle Aged
Immunogenicity, Vaccine
Young Adult
Vaccine Efficacy
Vietnam
Adolescent
mRNA Vaccines
Vaccines, Synthetic
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 May 2024
14 May 2024
Historique:
received:
05
09
2023
accepted:
16
04
2024
medline:
15
5
2024
pubmed:
15
5
2024
entrez:
14
5
2024
Statut:
epublish
Résumé
Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.
Identifiants
pubmed: 38744844
doi: 10.1038/s41467-024-47905-1
pii: 10.1038/s41467-024-47905-1
doi:
Types de publication
Journal Article
Randomized Controlled Trial
Clinical Trial, Phase I
Clinical Trial, Phase III
Clinical Trial, Phase II
Langues
eng
Sous-ensembles de citation
IM
Pagination
4081Informations de copyright
© 2024. The Author(s).
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