A Self-replicating COVID-19 mRNA Vaccine

A third messenger RNA (mRNA) vaccine appears to have proved its worth against COVID-19. This novel mRNA vaccine may come with significant advantages such as easier storage, along with lower cost because its “self-amplifying” design allows for smaller doses.

Arcturus Therapeutics, which staged a placebo-controlled trial of its candidate in more than 17,000 participants that the vaccine had 55% efficacy against symptomatic COVID-19 and provided 95% efficacy against severe illness and death. According to researchers, it is for the first time a self-amplifying RNA vaccine has been shown to be safe and effective. Arcturus’s success may also help make mRNA vaccines more broadly accessible. Its candidate incorporates a freeze-drying process to transform the mRNA-filled solution into a powder that can be stored at room temperature, and then rehydrated. This has far simpler cold-chain requirements than the conventional, liquid mRNA vaccines in use. The efficacy data has been submitted to the regulators for emergency use authorization.

Unlike the other available vaccines that contain mRNA that codes for the SARS-CoV-2 spike protein that delivers the mRNA to cells, which make copies of the spike and then clear the foreign genetic material within a few days, this Arcturus’s self-replicating enzyme has a different mechanism. The self-amplifying vaccine includes enzymes from alphaviruses to repeatedly copy the genetic strand inside a cell and stay in the body for more than twice as long.

Moreover, the conventional mRNA vaccine causes the replacement of the natural RNA building base-pair uridine with pseudouridine. Multiple studies have shown that this swapping leads to higher levels of the spike protein and lower production of immune chemicals called cytokines that can cause side effects. Thus this self-replicating mRNA vaccine against COVID-19 might be safer than the existing vaccines. However, thorough trials are warranted.

Content Source: Science.Org


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