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

• DOI: 10.1038/s41467-024-47905-1
• Publication Date: 2024-05-14T16:03:05Z
• Authors: 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 Ng...; 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
• Keywords: Male; 0301 basic medicine; Alternative medicine; Vaccine efficacy; Social Sciences; Infectious disease (medical specialty); FOS: Health sciences; Antibodies, Viral; Adverse effect; Immunogenicity, Vaccine; Pathology; Disease; Internal medicine; Immunology and Microbiology; Vaccines, Synthetic; Vaccines; Q; Vaccination; Life Sciences; Middle Aged; Immunogenicity; Clinical trial; Infectious Diseases; Vietnam; Health; Randomized controlled trial; Medicine; Female; mRNA Vaccines; Adult; COVID-19 Vaccines; Adolescent; Science; Immunobiology of Dendritic Cells; Immunology; Vaccine Efficacy; Coronavirus Disease 2019 Research; Article; Young Adult; 03 medical and health sciences; Health Sciences; Humans; Placebo; Antibody; Reactogenicity; SARS-CoV-2; FOS: Clinical medicine; COVID-19; Neutralizing antibody; Antibodies, Neutralizing; Coronavirus disease 2019 (COVID-19); Factors Affecting Vaccine Hesitancy and Acceptance

AbstractCombination 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.