Self-amplifying mRNA COVID-19 vaccine shows superiority over conventional mRNA vaccine

The U.S. biotech companies CSL and Arcturus Therapeutics announced yesterday that their self-amplifying messenger RNA (sa-mRNA) vaccine ARCT-154 (approved as Kostaive in Japan) elicited stronger and longer immunogenicity compared to Pfizer-BioNTech’s conventional mRNA vaccine Comirnaty against different strains of SARS-CoV-2, the virus that causes COVID-19.

A much lower dose of ARCT-154 (one-sixth of the Comirnaty dose) was needed to maintain a strong immune response that lasted up to one year.

ARCT-154 is the world’s first approved​ sa-mRNA vaccine. Self-amplifying mRNA addresses many of the challenges currently seen in mRNA vaccines, including high administration doses that lead to adverse effects, the need for repeated boosts with the same vaccine, and cold-chain storage.

Conventional mRNA vaccines encode a protein of interest – usually a protein found on the surface of a virus – to elicit an immune response. On the other hand, sa-mRNA vaccines are engineered​ to encode a gene of interest that contains instructions for the body to make more mRNA, resulting in a continuous expression of the protein of interest in the target cells. This induces an immune response at a much lower initial RNA dose than conventional mRNA vaccines.

The new data published by CSL and Arcturus​ compared their sa-mRNA vaccines to Comirnaty in two different studies. The first study, a randomized, double-blind, active-controlled Phase 3, enrolled adults, who had previously been fully immunized with three doses of mRNA vaccine(s). Trial participants then received a booster dose of the monovalent ARCT-154 or Comirnaty, upon which their immune responses against two of the main SARS-CoV-2 strains were measured at different time points across 12 months. The results showed that the immune response in recipients of ARCT-154 was superior to those people who received Comirnaty through all time points and against both strains.

"The 12-month results from the ARCT-154 study continue to establish the durability of immune response from this self-amplifying mRNA vaccine and reinforce the ability of this vaccine to provide protection against COVID-19 at lower doses compared to conventional mRNA vaccines," said Jonathan Edelman, M.D., Senior Vice President of the Vaccines Innovation Unit at CSL, in a press statement.

The second, six-month-long study, compared booster doses of bivalent Comirnaty with ARCT-2301, a bivalent formula that protects against the original SARS-CoV-2 strain and other, more recent variants. Here too, the results showed that ARCT-2301 elicited a superior antibody response compared to Comirnaty.

"The recent surge in COVID-19 infections and the emerging new variants illustrate the critical need for vaccines that provide a longer duration of protection compared to conventional mRNA vaccines," said Igor Smolenov, Chief Development Officer of Arcturus Therapeutics, in a press statement.

"These compelling new studies reaffirm that these sa-mRNA vaccines have the potential to offer potent protection against COVID-19."