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

Autor: Low JG; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore.; Department of Infectious Diseases, Singapore General Hospital, 169608, Singapore, Singapore.; Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore., de Alwis R; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore.; Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore., Chen S; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore., Kalimuddin S; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore.; Department of Infectious Diseases, Singapore General Hospital, 169608, Singapore, Singapore., Leong YS; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore.; Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore., Mah TKL; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore.; Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore., Yuen N; Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore.; Department of Biological Sciences, Nanyang Technological University, 639798, Singapore, Singapore., Tan HC; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore., Zhang SL; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore., Sim JXY; Department of Infectious Diseases, Singapore General Hospital, 169608, Singapore, Singapore., Chan YFZ; Department of Infectious Diseases, Singapore General Hospital, 169608, Singapore, Singapore., Syenina A; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore.; Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore., Yee JX; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore.; Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore., Ong EZ; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore.; Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore., Sekulovich R; Arcturus Therapeutics Inc, San Diego, CA, 92121, USA., Sullivan BB; Arcturus Therapeutics Inc, San Diego, CA, 92121, USA., Lindert K; Arcturus Therapeutics Inc, San Diego, CA, 92121, USA., Sullivan SM; Arcturus Therapeutics Inc, San Diego, CA, 92121, USA., Chivukula P; Arcturus Therapeutics Inc, San Diego, CA, 92121, USA., Hughes SG; Arcturus Therapeutics Inc, San Diego, CA, 92121, USA. drstevehughes@gmail.com., Ooi EE; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 8 College Road, 169857, Singapore, Singapore.; Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore.
Jazyk: angličtina
Zdroj: NPJ vaccines [NPJ Vaccines] 2022 Dec 13; Vol. 7 (1), pp. 161. Date of Electronic Publication: 2022 Dec 13.
DOI: 10.1038/s41541-022-00590-x
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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