Booster dose of self-amplifying SARS-CoV-2 RNA vaccine vs. mRNA vaccine: a phase 3 comparison of ARCT-154 with Comirnaty

Publication date: Jul 12, 2023

Background Licensed mRNA vaccines demonstrated initial effectiveness against COVID-19 but require booster doses to broaden the anti-SARS-CoV-2 response. There is an unmet need for novel highly immunogenic and broadly protective vaccines. We compared immunogenicity and tolerability of ARCT-154, a novel self-amplifying mRNA vaccine with the mRNA vaccine, Comirnaty. Methods We compared immune responses to ARCT-154 and Comirnaty booster doses in healthy 18-77-year-old Japanese adults initially immunised with two doses of mRNA COVID-19 vaccine (Comirnaty or Spikevax) then a third dose of Comirnaty at least 3 months previously. Neutralising antibodies were measured before and 28 days after booster vaccination. The primary objective was to demonstrate non-inferiority of the immune response against Wuhan-Hu-1 SARS-CoV-2 virus as geometric mean titre (GMT) ratios and seroresponse rates (SRR) of neutralising antibodies; key secondary endpoints included the immune response against the Omicron BA.4/5 variant and vaccine tolerability assessed using participant-completed electronic diaries. Findings Between December 13, 2022 and February 25, 2023 we enrolled 828 participants randomised 1:1 to receive ARCT-154 (n = 420) or Comirnaty (n = 408) booster doses. Four weeks after boosting, ARCT-154 induced higher Wuhan-Hu-1 neutralising antibodies GMTs than Comirnaty (5641 [95% CI: 4321-7363] and 3934 [2993-5169], respectively), a GMT ratio of 1.43 (95% CI: 1.26-1.63), with SRR of 65.2% (60.2-69.9) and 51.6% (46.4-56.8) meeting the non-inferiority criteria. Respective anti-Omicron BA.4/5 GMTs were 2551 (1687-3859) and 1958 (1281-2993), a GMT ratio of 1.30 (95% CI: 1.07-1.58), with SRR of 69.9% (65.0-74.4) and 58.0% (52.8-63.1), meeting the superiority criteria for ARCT-154 over Comirnaty. Booster doses of either ARCT-154 or Comirnaty were equally well-tolerated with no causally-associated severe or serious adverse events; 94.8% and 96.8% of ARCT-154 and Comirnaty vaccinees reported local reactions and 65.7% and 62.5% had solicited systemic adverse events. Events were mainly mild in severity, occurring and resolving within 3-4 days of vaccination. Interpretation Immune responses four weeks after an ARCT-154 booster dose in mRNA-immunised adults were higher than after a Comirnaty booster, meeting non-inferiority criteria against the prototype Wuhan-Hu-1 virus, and superiority criteria against the Omicron BA.4/5 variant.


Concepts Keywords
Japanese Adverse
July Arct
Nct05012943 Booster
Vaccines Comirnaty


Type Source Name
disease VO dose
disease VO RNA vaccine
disease VO vaccine
disease VO ARCT-154
disease VO Comirnaty
disease VO effectiveness
disease MESH COVID-19
disease VO COVID-19 vaccine
disease VO vaccination
disease IDO immune response
disease VO USA
drug DRUGBANK Coenzyme M
disease MESH infections
disease VO effective
disease VO Glycoprotein
disease VO protocol
disease IDO blood
disease IDO infection
disease IDO history
disease MESH chronic infection
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease MESH myocarditis
disease MESH pericarditis
disease MESH cardiomyopathy
disease MESH equine encephalitis
disease VO injection
drug DRUGBANK Etoperidone
disease MESH erythema
disease MESH arthralgia
disease MESH chest pain
disease VO adverse event
disease VO report
disease VO vaccination protocol
disease VO time
disease MESH high blood pressure
drug DRUGBANK Methionine
disease MESH foot deformity
disease IDO site
disease MESH nasopharyngitis
disease VO population
disease MESH sequelae
drug DRUGBANK Spinosad
disease MESH breakthrough infections
disease VO vaccine effectiveness
disease VO Viruses
disease MESH infectious diseases
disease MESH cancer
disease MESH influenza
disease IDO infectivity
drug DRUGBANK Adenosine 5′-phosphosulfate
disease VO age
disease MESH allergic reaction
disease MESH convulsions
disease IDO assay
disease MESH Death

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