Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials

Autor: Nhân Thị Hồ, Steven G. Hughes, Van Thanh Ta, Lân Trọng Phan, Quyết Đỗ, Thượng Vũ Nguyễn, Anh Thị Văn Phạm, Mai Thị Ngọc Đặng, Lượng Viết Nguyễn, Quang Vinh Trịnh, Hùng Ngọc Phạm, Mến Văn Chử, Toàn Trọng Nguyễn, Quang Chấn Lương, Vy Thị Tường Lê, Thắng Văn Nguyễn, Lý-Thi-Lê Trần, Anh Thi Van Luu, Anh Ngoc Nguyen, Nhung-Thi-Hong Nguyen, Hai-Son Vu, Jonathan M. Edelman, Suezanne Parker, Brian Sullivan, Sean Sullivan, Qian Ruan, Brenda Clemente, Brian Luk, Kelly Lindert, Dina Berdieva, Kat Murphy, Rose Sekulovich, Benjamin Greener, Igor Smolenov, Pad Chivukula, Vân Thu Nguyễn, Xuan-Hung Nguyen
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-024-47905-1
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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