Longer-Lasting Immunity with sa-mRNA Vaccine vs. Standard mRNA Booster

A recent study by Meiji Seika Pharma in Japan has revealed that the self-amplifying messenger RNA (sa-mRNA) COVID-19 vaccine, ARCT-154, provides a more enduring immune response compared to traditional mRNA vaccines. This breakthrough was announced by CSL Behring and Arcturus Therapeutics, who conducted a Phase 3 follow-up study on the booster dose of ARCT-154. Notably, ARCT-154 was given at a significantly lower dosage than Comirnaty® (5 μg versus 30 μg).

The six-month post-vaccination analysis showed that ARCT-154 not only induced a longer-lasting immune response against both the Wuhan strain and the Omicron BA.4/5 variant but also demonstrated superior antibody persistence. Jonathan Edelman, Senior Vice President of CSL's Vaccines Innovation Unit, emphasized the importance of prolonged protection against COVID-19 at lower doses, a key attribute of sa-mRNA technology.

Pad Chivukula, Chief Scientific Officer of Arcturus Therapeutics, highlighted the innovative nature of this vaccine technology, which has the potential to offer significant improvements over conventional mRNA vaccines, particularly in terms of sustained protection at reduced dosages.

The study, which was randomized, double-blind, and active-controlled, was carried out across 11 sites in Japan. It evaluated the immunogenicity of ARCT-154 and Comirnaty® at one, three, and six months post-booster. Participants with recent COVID-19 infection, as indicated by seropositivity for SARS-CoV-2 N-protein, were excluded from the analysis, resulting in 332 and 313 participants in the ARCT-154 and Comirnaty® groups, respectively.

At the start of the study, both groups had comparable geometric mean titers (GMTs) against the Wuhan-Hu-1 strain. However, one month post-booster, ARCT-154 showed a higher immune response with a GMT of 5390 compared to Comirnaty®'s GMT of 3738. This trend continued at three months post-booster, with ARCT-154 maintaining a higher GMT ratio of 2.04. By Day 181, the GMTs for ARCT-154 remained significantly higher than those for Comirnaty®, indicating a slower decline in antibodies.

The study also observed a similar pattern of superior immunogenicity and slower decline in Omicron BA.4/5 neutralizing antibodies for ARCT-154. The GMTs were comparable at baseline but increased significantly post-booster for ARCT-154, and the advantage was maintained up to Day 181.

Self-amplifying mRNA vaccines, unlike standard mRNA vaccines, instruct the body to produce more mRNA and protein, thereby enhancing the immune response. This technology is a significant advancement in the field of vaccine development.

CSL is a global biotechnology company with a diverse range of life-saving medicines, including treatments for hemophilia, immune deficiencies, influenza vaccines, and therapies for iron deficiency and nephrology. Arcturus Therapeutics is a late-stage clinical mRNA medicines and vaccines company with enabling technologies such as LUNAR® lipid-mediated delivery and STARR® mRNA Technology. Meiji Seika Pharma has been a leader in providing pharmaceutical products for infectious diseases, central nervous system diseases, and generic drugs since 1946.

The study's findings are a testament to the potential of sa-mRNA technology in offering longer-lasting and more effective protection against COVID-19, marking a significant step forward in the ongoing fight against the pandemic.