New COVID-19 sa-mRNA Vaccine

Regulators in Japan have given a green light to a COVID-19 vaccine that uses self-amplifying messenger RNA (sa-mRNA), the first vaccine of this kind to get full approval.

The ARCT-154 vaccine was co-developed by Arcturus Therapeutics and CSL. The innovative sa-mRNA vaccine enables host cells in the body to make copies of the mRNA which encodes viral replicase genes in addition to immunogenic genes. ARCT-154 uses mRNAs encoding replicase components of the Venezuela equine encephalitis virus and the spike glycoprotein of the SARS-CoV-2 D614G variant enclosed in a proprietary lipid nanoparticle. The self-replicative activity of sa-mRNA vaccines enables them to be used at lower concentrations than conventional mRNA vaccines to achieve similar or better antigen expression, meaning they could be safer and manufactured at large scale.

The approval by Japan’s Ministry of Health is based on various phase 3 study results, including a COVID-19 booster trial with 5 μg ARCT-154 that resulted in higher immune responses than with 30 μg Comirnaty (Pfizer/BioNTech). In previously vaccinated adults, 70% of those boosted with ARCT-154 developed antibodies against Omicron BA.4/5, compared with 58% of those boosted with Comirnaty. And antibody titres were higher at 28 days in people who received ARCT-154. Both vaccines were equally well tolerated.

Arcturus and CSL have also filed ARCT-154 for European regulatory approval. The companies have additional sa-mRNA vaccine candidates against other SARS-Cov-2 variants in clinical testing, as have companies such as ImmunityBio and Gritstone Bio. Another sa-RNA vaccine called Gemcovac-19, manufactured by Gennova Biopharmaceuticals, was approved in India in June 2022, but for emergency use only. Vaccine candidates using sa-mRNA are also in clinical trials for influenza.

https://www.nature.com/articles/s41587-023-02101-2