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

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.

COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2

“…We observed a predominant response to the boosting dose, this contrasts to a recent pre-print of the Arcturus saRNA COVID-19 Phase 1/2 vaccine trial where the predominant response was elicited by the priming dose with limited benefit of a boosting dose reaching binding antibody levels overlapping but not above those of convalescent subjects. 14 …”

COVAC1 Phase 2a Expanded Safety and Immunogenicity Study of a Self-Amplifying RNA Vaccine Against SARS-CoV-2

“…We observed a predominant response to the boosting dose, this contrasts to a recent pre-print of the Arcturus saRNA COVID-19 Phase 1/2 vaccine trial where the predominant response was elicited by the priming dose with limited benefit of a boosting dose reaching binding antibody levels overlapping but not above those of convalescent subjects. 14 Binding IgG antibody responses against S were more frequent in the expanded safety cohort, although seroconversion rates were still not 100%. Binding antibody responses against S correlate with vaccine efficacy against symptomatic COVID-19.…”

Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development

“…Another VEEV-based saRNA vaccine candidate (ARTC-021) expressing the SARS-CoV-2 spike glycoprotein was also found to be safe and had a 100% seroconversion rate. Anti-spike IgG titers were equal to those in COVID-19 convalescent plasma [ 142 ]. A larger clinical trial is currently ongoing with ARTC-021 as a booster vaccine (NCT05012943).…”