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

• Main Authors: Low, Jenny G., de Alwis, Ruklanthi, Chen, Shiwei, Kalimuddin, Shirin, Leong, Yan Shan, Mah, Tania Ken Lin, Yuen, Natalene, Tan, Hwee Cheng, Zhang, Summer L., Sim, Jean X. Y., Chan, Yvonne F. Z., Syenina, Ayesa, Yee, Jia Xin, Ong, Eugenia Z., Sekulovich, Rose, Sullivan, Brian B., Lindert, Kelly, Sullivan, Sean M., Chivukula, Pad, Hughes, Steven G., Ooi, Eng Eong
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Biological sciences; SARS-CoV-2 Vaccine; Neutralizing Antibody
• Online Access: https://hdl.handle.net/10356/169469
• Institution: Nanyang Technological University

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.