First self-amplifying mRNA type coronavirus vaccine approved in Japan

At the end of November, Japan’s Ministry of Health, Labor and Welfare (MHLW) granted approval for the self-amplifying messenger RNA (sa-mRNA) coronavirus vaccine ARCT-154 for initial and booster vaccination in adults aged 18 years and older. . Arcturus Therapeutics has an exclusive partnership with CSL’s vaccine subsidiary, his CSL Seqirus, to manufacture the ARCT-154 vaccine. The companies are developing new mRNA vaccines against COVID-19 and influenza.¹

Jonathan Edelman, M.D., senior vice president of CSL’s Vaccine Innovation Unit, said: “Today’s approval is a historic and exciting milestone as the world’s first registered SA-mRNA vaccine, protecting global public health. This confirms CSL’s commitment to: In a statement. “We are committed to working with health authorities around the world to ensure this important vaccine technology is available to people at risk from COVID-19.” ¹

The approval is based on positive clinical data from several studies, including a 16,000-subject efficacy study and a booster study conducted in Vietnam. In previous reports, infectious diseasetopline data from the booster study showed higher immunogenicity results and a favorable safety profile compared to standard mRNA COVID-19 vaccine comparators.

This booster study is a phase 1/2 randomized, observer-blind study conducted in both the United States and Singapore, and is a preliminary series of approved novel coronavirus disease (COVID-19) mRNA vaccines. Thirty-six vaccinated adult participants were included.

Participants were randomized 1:1:1 to receive one booster dose of either ARCT-021, ARCT-154, or ARCT-165 vaccine on day 1. These vaccines all encode the full-length S glycoprotein of SARS-CoV-2, which is the native conformational ancestral strain, the prefusion stabilized B1 variant containing the D614G mutation, or the beta variant, respectively. Immunogenicity was assessed as neutralizing antibody titers against the SARS-CoV-2 D614G strain, and a panel of mutants was subjected to pseudovirus microneutralization assays on days 1, 15, 29, 91, 181, 271, and 366. measured by.

All three vaccines showed significant improvement against the D614G variant at day 29 with geometric mean fold increases (GMFR) of 20.0, 36.7, and 23.5 from prebooster levels after ARCT-021, ARCT-154, and ARCT-165, respectively. induced a strong neutralizing immune response. The lead candidate, ARCT-154, induced a broad cross-neutralizing immune response that was sustained up to 1 year post-boost even without boosting. Similar trends were observed for other variants such as Beta, Delta, Omicron BA1, Omicron BA2, and Omicron BA4/5. Additional exploratory testing confirmed cross-neutralization against the emerging BQ11 and XBB15 omicron sublineages with GMFRs of 12.8 and 3.4, respectively, 29 days post-boost.

sa-mRNA platform

Messenger RNA (mRNA) vaccine platforms fight infections by instructing cells in the body to produce specific proteins, stimulating an immune response and leaving a blueprint for recognizing and fighting future infections. I will protect myself. However, sa-mRNA makes copies of mRNA and generates more protein production compared to the equivalent amount of mRNA in the vaccine. The companies report that this technology has the potential to elicit a stronger cellular immune response and extend the duration of protection while using significantly lower doses of mRNA.¹

reference

1. Japan’s Ministry of Health, Labor and Welfare has approved CSL and Arcturus Therapeutics’ ARCT-154, the first self-amplifying mRNA vaccine approved for COVID-19 for adults. press release. November 28, 2023. https://www.prnewswire.com/news-releases/japans-ministry-of-health-labour-and-welfare-approves-csl-and-arcturus-therapeutics-arct-154-the-first -self-amplification-mrna -Vaccines-Approved-New Coronavirus-Adult-301999193.html