Immunogenicity and safety of self-amplifying mRNA COVID-19 vaccine (ARCT-2303), with or without co-administration of seasonal inactivated influenza vaccine in adults: a phase 3, randomised, controlled, observer-blind, multicentre study.
rct · Level I
Where this comes from
- Record sourced from PubMed, PMID 40896462.
- Also identified by DOI 10.1016/j.eclinm.2025.103428 and PMC identifier 12396474.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
A recently licenced self-amplifying mRNA (sa-mRNA) COVID-19 vaccine induces a robust, broad, and long-lasting immune response, extending the arsenal of efficacious COVID-19 countermeasures. We ran a clinical study to assess the benefits of vaccine strain update and the feasibility of co-administration with influenza vaccines. Between March 27, 2024 and April 10, 2025, we performed a randomised, observer-blind, placebo-controlled, phase 3 study with 1499 adult participants to compare immune responses of sa-mRNA vaccine, encoding spike glycoprotein of the XBB.1.5 subvariant (ARCT-2303), with vaccine encoding the ancestral strain (ARCT-154), as measured by geometric mean titres of neutralising antibodies and SARS-CoV-2 neutralising antibody seroconversion rates against the Omicron XBB.1.5, and to assess the immunological non-inferiority of co-administered ARCT-2303 and influenza vaccines compared with separately administered vaccines, as measured by neutralising antibodies against Omicron XBB.1.5.6 and haemagglutinin inhibition against influenza vaccine strains. Reactogenicity (adverse events on Days 1-7) and safety (adverse events on Days 1-181) were also assessed. The trial was registered on ClinicalTrials.gov (identifier NCT06279871). The geometric mean ratio (ARCT-2303/ARCT-154) of neutralising antibodies against Omicron XBB.1.5.6 on Day 29 was 2.7 (95% confidence interval (CI): 2.3-3.2), and the seroconversion rate difference was 28.4% (21.8-34.9); both met the prespecified superiority criteria. Concomitant administration of ARCT-2303 had no impact on the immune response to the quadrivalent influenza vaccine antigens, whether the non-adjuvanted vaccine given to 18‒64 year-old adults or the adjuvanted vaccine given to adults 65 years and older. The non-inferiority of the immune response against Omicron XBB.1.5.6 was also demonstrated when ARCT-2303 was co-administered or administered separately. We conclude that ARCT-2303 induces a robust immune response against the vaccine variant of SARS-CoV-2 and can be co-administered with licenced influenza vaccines in adults with no impact on the safety or immunogenicity of either vaccine. The study is funded by CSL under a collaboration agreement with Arcturus Therapeutics.