Immunogenicity and safety of a booster dose of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2 mRNA COVID-19 vaccine: a double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial

Licensed mRNA COVID-19 vaccines require booster doses to sustain SARS-CoV-2-specific responses, creating the need for novel, broadly immunogenic vaccines. We aimed to compare the immunogenicity, safety, and tolerability of ARCT-154—a self-amplifying mRNA vaccine against SARS-CoV-2 D614G variant—with the BNT162b2 (Comirnaty; Pfizer–BioNTech) mRNA vaccine when administered as a fourth-dose booster. This double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial, conducted at 11 outpatient clinical sites in Japan, enrolled healthy adults aged at least 18 years who had previously been immunised with two doses of an mRNA COVID-19 vaccine (BNT162b2 or mRNA-1273 [Spikevax; Moderna]) followed by a third dose of BNT162b2 at least 3 months before enrolment. Participants were randomly assigned, in a 1:1 ratio using an Interactive Response Technology system with a block size of four, and with stratification by age (18–64 years or ≥65 years) and by interval since last COVID-19 vaccination (