Safety and immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine

Abstract

Combination of waning immunity and lower effectiveness of approved COVID-19 vaccines against SARS-CoV-2 variants necessitates new vaccines. We evaluated the safety, immunogenicity and efficacy of a novel self-amplifying mRNA COVID-19 vaccine against the D614G variant, ARCT-154, in an integrated phase 1/2/3a/3b, randomized, observer-blind trial in Vietnamese adults. Two doses of ARCT-154 or placebo 28 days apart were well tolerated with mild to moderate transient adverse events. Four weeks after the second dose 94.1% (95% CI: 92.1–95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline titers of 14.5 (95% CI: 13.6–15.5). Most cases of confirmed COVID-19 eligible for efficacy analysis were due to the Delta variant. Absolute efficacy of ARCT-154 was 56.6% (95% CI: 48.7–63.3) against any COVID-19, and 95.3% (80.5–98.9) against severe COVID-19. We show ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease and COVID-associated death.

mRNA vaccine designs for optimal adjuvanticity and delivery

“…Furthermore, dsRNA intermediates during intracellular proliferation may also enhance cellular dsRNA receptor activation to induce innate immune responses. These features enable effective vaccination in animals and humans using low doses of saRNA [ 97 , 98 ]. However, the persistence of dsRNA intermediates may cause prolonged immunostimulation and PKR activation, potentially posing negative impacts on vaccination outcomes in some settings.…”