COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2

Szubert, Alex J.; Pollock, Katrina M; Cheeseman, Hannah; Alagaratnam, Jasmini; Bern, Henry; Bird, Olivia; Boffito, Marta; Byrne, Ruth A.; Cole, Tom; Cosgrove, Catherine; Faust, Saul N.; Fidler, Sarah; Galiza, Eva; Hassanin, Hana; Kalyan, Mohini; Libri, Vincenzo; McFarlane, Leon R.; Milinkovic, Ana; O’Hara, Jessica; Owen, David R.; Owens, Daniel R; Pacurar, Mihaela; Rampling, Tommy; Skene, Simon; Winston, Alan; Woolley, James; Yim, Yee Ting Nicole; Dunn, David; McCormack, Sheena; Shattock, Robin J.

doi:10.1016/j.eclinm.2022.101823

Cited by 20 publications

(11 citation statements)

References 17 publications

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“…It remains to be seen whether ARCT-154 induces similar responses in humans. In adults from 18-75 years of age Szubert et al found 1 μg and 10 μg doses of an investigational lipid encapsulated SARS-CoV-2 sa-RNA vaccine induced neutralizing and anti-spike-IgG antibodies although there was only a modest correlation between the two measures 31 – 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Enrolled volunteers in phases 1/2/3a were randomized 3:1 and those in phase 3b 1:1 to receive ARCT-154 or placebo. Phase 3b included volunteers at increased risk of severe COVID-19 due to their comorbidity status 31 or being ≥ 60 years old, and randomization included stratification of these at-risk participants. Phase 1 participants were recruited and treated first, parallel enrolment for phases 2 and 3a was only allowed after the DSMB and Vietnam MoH had reviewed all safety data collected up to 7 days after the second vaccination (Day 36) in phase 1.…”

Section: Methodsmentioning

confidence: 99%

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Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials

Hồ,

Hughes,

et al. 2024

Nat Commun

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Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild–moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1–95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6–15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7– 63.3) against any COVID-19, and 95.3% (80.5–98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials

Hồ,

Hughes,

et al. 2024

Nat Commun

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“…A phase II trial of COVAC1 was conducted in the UK to expand the safety and immunogenicity study of this vaccine [ 98 ]. In this case, a prolonged interval of 14 weeks was maintained between prime and boost, with a 1 μg dose followed by a 10 μg dose.…”

Section: Sarna-based Covid-19 Vaccines In Clinical Trialsmentioning

confidence: 99%

“…In general, saRNA vaccines based on LNPs have shown a certain degree of reactogenicity associated to the dose, with a higher proportion of local reactions and adverse effects in those individuals receiving 10 μg, but with a very good tolerability when using doses of 1 µg or less [ 55 ]. An inverse association of reactogenicity and age has also been described, with adverse reactions being less frequent at older ages [ 98 ]. It is possible that the use of delivery vehicles different from LNPs, such as LION, could reduce the reactogenicity of these vaccines [ 56 ].…”

Section: Sarna-based Covid-19 Vaccines In Clinical Trialsmentioning

confidence: 99%

Self-Amplifying RNA: A Second Revolution of mRNA Vaccines against COVID-19

Silva-Pilipich,

Beloki,

Salaberry

et al. 2024

Vaccines

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SARS-CoV-2 virus, the causative agent of COVID-19, has produced the largest pandemic in the 21st century, becoming a very serious health problem worldwide. To prevent COVID-19 disease and infection, a large number of vaccines have been developed and approved in record time, including new vaccines based on mRNA encapsulated in lipid nanoparticles. While mRNA-based vaccines have proven to be safe and effective, they are more expensive to produce compared to conventional vaccines. A special type of mRNA vaccine is based on self-amplifying RNA (saRNA) derived from the genome of RNA viruses, mainly alphaviruses. These saRNAs encode a viral replicase in addition to the antigen, usually the SARS-CoV-2 spike protein. The replicase can amplify the saRNA in transfected cells, potentially reducing the amount of RNA needed for vaccination and promoting interferon I responses that can enhance adaptive immunity. Preclinical studies with saRNA-based COVID-19 vaccines in diverse animal models have demonstrated the induction of robust protective immune responses, similar to conventional mRNA but at lower doses. Initial clinical trials have confirmed the safety and immunogenicity of saRNA-based vaccines in individuals that had previously received authorized COVID-19 vaccines. These findings have led to the recent approval of two of these vaccines by the national drug agencies of India and Japan, underscoring the promising potential of this technology.

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“…In phase I, the LNP-nCoVsaRNA vaccine was safe, well tolerated, and elicited specific immune responses but failed to reach 100% seroconversion rates [ 110 ]. However, in phase II, superior seroconversion rates were achieved by either a prolonged dosing interval or the administration of a 1.0 μg prime dose followed by a 10 μg booster dose [ 111 ]. Another similar nanostructural lipid carrier (NLC)-encapsulated VEE-based saRNA vaccine containing the SARS-CoV-2 S RNA induced robust Th1-biased T-cell responses in immunized mice [ 166 ].…”

Section: Covid-19 Vaccinesmentioning

confidence: 99%

COVID-19 Vaccines: Where Did We Stand at the End of 2023?

Lundstrom

2024

Viruses

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Vaccine development against SARS-CoV-2 has been highly successful in slowing down the COVID-19 pandemic. A wide spectrum of approaches including vaccines based on whole viruses, protein subunits and peptides, viral vectors, and nucleic acids has been developed in parallel. For all types of COVID-19 vaccines, good safety and efficacy have been obtained in both preclinical animal studies and in clinical trials in humans. Moreover, emergency use authorization has been granted for the major types of COVID-19 vaccines. Although high safety has been demonstrated, rare cases of severe adverse events have been detected after global mass vaccinations. Emerging SARS-CoV-2 variants possessing enhanced infectivity have affected vaccine protection efficacy requiring re-design and re-engineering of novel COVID-19 vaccine candidates. Furthermore, insight is given into preparedness against emerging SARS-CoV-2 variants.

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COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2

Cited by 20 publications

References 17 publications

Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials

Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials

Self-Amplifying RNA: A Second Revolution of mRNA Vaccines against COVID-19

COVID-19 Vaccines: Where Did We Stand at the End of 2023?

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