npj Vaccines (Dec 2022)

A phase I/II randomized, double-blinded, placebo-controlled trial of a self-amplifying Covid-19 mRNA vaccine

  • Jenny G. Low,
  • Ruklanthi de Alwis,
  • Shiwei Chen,
  • Shirin Kalimuddin,
  • Yan Shan Leong,
  • Tania Ken Lin Mah,
  • Natalene Yuen,
  • Hwee Cheng Tan,
  • Summer L. Zhang,
  • Jean X. Y. Sim,
  • Yvonne F. Z. Chan,
  • Ayesa Syenina,
  • Jia Xin Yee,
  • Eugenia Z. Ong,
  • Rose Sekulovich,
  • Brian B. Sullivan,
  • Kelly Lindert,
  • Sean M. Sullivan,
  • Pad Chivukula,
  • Steven G. Hughes,
  • Eng Eong Ooi

DOI
https://doi.org/10.1038/s41541-022-00590-x
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 9

Abstract

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Abstract Coronavirus disease-19 (Covid-19) pandemic have demonstrated the importantance of vaccines in disease prevention. Self-amplifying mRNA vaccines could be another option for disease prevention if demonstrated to be safe and immunogenic. Phase 1 of this randomized, double-blinded, placebo-controlled trial (N = 42) assessed the safety, tolerability, and immunogenicity in healthy young and older adults of ascending levels of one-dose ARCT-021, a self-amplifying mRNA vaccine against Covid-19. Phase 2 (N = 64) tested two-doses of ARCT-021 given 28 days apart. During phase 1, ARCT-021 was well tolerated up to one 7.5 μg dose and two 5.0 μg doses. Local solicited AEs, namely injection-site pain and tenderness were more common in ARCT-021vaccinated, while systemic solicited AEs, mainly fatigue, headache and myalgia were reported in 62.8% and 46.4% of ARCT-021 and placebo recipients, respectively. Seroconversion rate for anti-S IgG was 100% in all cohorts, except for the 1 μg one-dose in younger adults and the 7.5 μg one-dose in older adults. Anti-S IgG and neutralizing antibody titers showed a general increase with increasing dose, and overlapped with titers in Covid-19 convalescent patients. T-cell responses were also observed in response to stimulation with S-protein peptides. Taken collectively, ARCT-021 is immunogenic and has favorable safety profile for further development.