The success of mRNA Covid vaccines from Pfizer and Moderna has been apparent, but they come with limitations such as short lifetimes and cold chain requirements. Two newly reported vaccines, GEMCOVAC-OM and ARCT-154, use self-amplifying RNA technology to overcome these hurdles. These vaccines may herald a new era of coronavirus vaccination due to their promising results in recent human trials.
Self-amplifying RNA vaccines contain replicase enzymes that can create multiple copies of the RNA strand, resulting in significantly higher protein levels than traditional vaccines. The self-amplifying nature of these vaccines also stimulates the innate immune system, providing a built-in adjuvant effect. Furthermore, self-amplifying RNA vaccines can achieve the same or better immune responses with lower doses compared to regular mRNA vaccines.
GEMCOVAC-OM and ARCT-154 are two self-amplifying RNA vaccines that have shown impressive results in human trials. GEMCOVAC-OM, developed in India, demonstrated significantly higher anti-Omicron IgG antibody responses compared to the AstraZeneca vaccine in a randomized controlled trial. ARCT-154, developed by Arcturus Therapeutics, outperformed the Pfizer vaccine in a study in Japan over six months, particularly against more current strains of SARS-CoV-2.
Both vaccines have the advantage of being lyophilized, allowing for stability at 2-9 degrees Celsius for up to 12 months without super-cold storage. This eliminates the need for extensive cold chain requirements, making the vaccines more accessible in low-resource countries. Additionally, self-amplifying RNA vaccines do not require modified nucleotides like pseudouridine, which may cause misreading by ribosomes and autoimmune responses.
GEMCOVAC-OM and ARCT-154 also differ in their administration methods, with the former injected intradermally and the latter injected intramuscularly. Intradermal delivery may present antigens more naturally and lead to a more mature immune response. These vaccines offer many advantages beyond Covid protection, such as long-term stability, the potential for broader protection against various diseases, and the maturation of multiple immune cell types.
Overall, the promising results from human trials of GEMCOVAC-OM and ARCT-154 demonstrate the potential of self-amplifying RNA vaccines to address the limitations of traditional mRNA vaccines. These advancements could pave the way for more effective and accessible vaccination strategies not only for Covid but also for other diseases in the future.
