Persistence of immune responses of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2

Despite their high efficacy against the original Wuhan-Hu-1 strain and early SARS-CoV-2 variants, mRNA vaccines elicit a relatively short duration of immunity, exacerbated by immune evasion by variants leading to lower efficacy;1 for example, mRNA vaccine effectiveness against omicron declined to below 20% within 6 months of vaccination.2 Additionally, new variants are continuing to emerge,3 so the ongoing risk of COVID-19 outbreaks due to persistent viral circulation necessitates ongoing development of new vaccines to prolong vaccine-induced immunity, ideally for at least 1 year to meet new annual immunisation recommendations.3 We recently reported that a booster dose of the novel mRNA vaccine, ARCT-154 (Arcturus Therapeutics Holdings, San Diego, CA, USA), a self-amplifying mRNA (saRNA) vaccine based on the SARS-CoV-2 D614G variant (B.1), induced superior immunogenicity than BNT162b2 (Comirnaty; Pfizer–BioNTech) in BNT162b2-primed adults 1 month after administration.4 Commenting on our Article, Herfst and de Vries5 noted that “whether this [improvement in RNA vaccine technology] leads to better and longer-lasting immunity warrants further investigation”. In our study, Japanese adults who had been primed with two doses of mRNA vaccine and a booster dose of BNT162b2 at least 3 months earlier were randomly assigned equally to receive a second booster of either ARCT-154 (n=420) or BNT162b2 (n=408).4 In this extension analysis, we progressively excluded any participant who displayed seropositivity on days 1, 29, 91, or 181 for SARS-CoV-2 N-protein, considered to be indicative of COVID-19 infection, leaving 332 in the ARCT-154 group and 313 participants in the BNT162b2 group eligible for inclusion at the 6-month timepoint (appendix). [...]ARCT-154 contains 5 μg of mRNA, as compared with 30 μg in BNT162b2, suggesting potential dose sparing with saRNA vaccines.