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

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NPJ Vaccines


. 2022 Dec 13;7(1):161.
doi: 10.1038/s41541-022-00590-x.
A phase I/II randomized, double-blinded, placebo-controlled trial of a self-amplifying Covid-19 mRNA vaccine


Jenny G Low ^{# 1 2 3} , Ruklanthi de Alwis ^{# 1 3} , Shiwei Chen ¹ , Shirin Kalimuddin ^{1 2} , Yan Shan Leong ^{1 3} , Tania Ken Lin Mah ^{1 3} , Natalene Yuen ^{3 4} , Hwee Cheng Tan ¹ , Summer L Zhang ¹ , Jean X Y Sim ² , Yvonne F Z Chan ² , Ayesa Syenina ^{1 3} , Jia Xin Yee ^{1 3} , Eugenia Z Ong ^{1 3} , Rose Sekulovich ⁵ , Brian B Sullivan ⁵ , Kelly Lindert ⁵ , Sean M Sullivan ⁵ , Pad Chivukula ⁵ , Steven G Hughes ⁶ , Eng Eong Ooi ^{1 3}



Affiliations

• PMID: 36513697
• DOI: 10.1038/s41541-022-00590-x

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.