Nature Communications (May 2024)

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

  • 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

DOI
https://doi.org/10.1038/s41467-024-47905-1
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 13

Abstract

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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.