A randomized trial comparing safety, immunogenicity and efficacy of self-amplifying mRNA and adenovirus-vector COVID-19 vaccines

Abstract

This phase 3 trial compared safety, tolerability, immunogenicity and efficacy of the self-amplifying mRNA COVID-19 vaccine, ARCT-154, with ChAdOx1-S adenovirus-vector vaccine. In four centers in Vietnam adult participants aged 18‒85 years were randomly assigned to receive two doses, 28 days apart, of either ARCT-154 (n = 1186) or ChAdOx1-S (n = 1180). Both vaccines were well tolerated with similar safety and reactogenicity profiles consisting of mainly mild-to-moderate solicited adverse events and few related serious adverse events. Higher neutralizing antibody responses persisting to one-year post-vaccination after ARCT-154 compared with ChAdOx1-S were associated with a generally higher efficacy against COVID-19. In an exploratory analysis relative vaccine efficacy of ARCT-154 vs. ChAdOx1-S against any COVID-19 from Day 36 to Day 394 was 19.8% (95% CI: 4.0-33.0). Self-amplifying mRNA vaccine offers potential immunological advantages in terms of immunogenicity and efficacy over adenovirus-vector vaccine without compromising safety.

Fig. 1. Study flow chart.

Numbers of volunteers screened and participants enrolled in ARCT-154 and ChAdOx1-S groups at each study milestone and analysis sets are displayed. mITT modified intention-to-treat, SAS safety analysis set.

Fig. 2. Solicited reactogenicity.

The percentages of each study group reporting the solicited local reactions and systemic adverse events are displayed according to severity.

Fig. 3. Neutralizing antibody responses.

Geometric mean titers of neutralizing antibody responses against Wuhan-Hu1 strain measured by CPE-based microneutralization assay (1/dil) after doses 1 (Day 1) and 2 (Day 29) of ARCT-154 or ChAdOx1-S, in baseline anti-N-protein naive subjects, according to N-protein seropositivity status on Day 394. Chart shows geometric mean titers (95% CI) with n values for each time point, and table shows the GMT ratio between ARCT-154 and ChAdOx1-S groups and the geometric mean-fold rises at each time point (with 95% CI).

Fig. 4. Cumulative incidence of COVID-19 cases.

Relative vaccine efficacy (rVE) of ARCT-154 vs. ChAdOx1-S vaccine against any severity of COVID-19 from Day 36 (one week after the second dose) up to Day 92 (A) and from Day 36 up to Day 211 (B).