ABSTRACT
Introduction:Prior to the emergence of SARS-CoV-2, the potential use of mRNA vaccines for a rapid pandemic response had been well described in the scientific literature, however during the SARS-CoV-2 outbreak we witnessed the large-scale deployment of the platform in a real pandemic setting. Of the three RNA platforms evaluated in clinical trials, including 1) conventional, non-amplifying mRNA (mRNA), 2) base-modified, non-amplifying mRNA (bmRNA), which incorporate chemically modified nucleotides, and 3) self-amplifying RNA (saRNA), the bmRNA technology emerged with superior clinical efficacy.
Areas covered:This review describes the current state of these mRNA vaccine technologies, evaluates their strengths and limitations, and argues that saRNA may have significant advantages if the limitations of stability and complexities of manufacturing can be overcome.
Expert opinion:The success of the SARS-CoV-2 mRNA vaccines has been remarkable. However, several challenges remain to be addressed before this technology can successfully be applied broadly to other disease targets. Innovation in the areas of mRNA engineering, novel delivery systems, antigen design, and high-quality manufacturing will be required to achieve the full potential of this disruptive technology.
Article highlights
The cell-free and platform nature of the RNA technology can accelerate product development and mass-manufacturing
The saRNA vaccine platform holds promises for longer duration transgene expression, co-expression of multiple transgenes, lower RNA amount per dose, and enhanced adjuvant effect, as well as enhanced antigen-specific adaptive immunity
The manufacturing productivity of the saRNA vaccine platform may be two orders of magnitude higher than the productivity of the mRNA vaccine platform
The manufacturing saRNA cost per dose may be one order of magnitude lower than the mRNA cost per dose
Manufacturing challenges for producing the longer and less stable saRNA vaccines have to be addressed, if the full potential of the technology is to be realized
The undesired innate immune stimulation must be reduced by removing impurities during RNA manufacture, by vector engineering and by delivery system optimization.
Declaration of interest
A. Geall is a shareholder in Replicate Bioscience. J. Ulmer is a shareholder in TechImmune LLC and Immorna Biotherapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Notes
1. A saRNA manufactured by Gennova Biopharmaceuticals – GEMCOVAC-19 – recently received emergency use authorization(EUA) from the office of the Drugs Controller General of India (DCGI).https://health.economictimes.indiatimes.com/news/pharma/gennova-biopharmaceuticals-mrna-covid-19-vaccine-receives-eua-from-dcgi/92539102?utm_source=whatsapp_web&utm_medium=social&utm_campaign=socialsharebuttons