Self-amplifying mRNA-Based Vaccine Technology and Its Mode of Action

Abstract

Self-amplifying mRNAs derived from the genomes of positive-strand RNA viruses have recently come into focus as a promising technology platform for vaccine development. Non-virally delivered self-amplifying mRNA vaccines have the potential to be highly versatile, potent, streamlined, scalable, and inexpensive. By amplifying their genome and the antigen encoding mRNA in the host cell, the self-amplifying mRNA mimics a viral infection, resulting in sustained levels of the target protein combined with self-adjuvanting innate immune responses, ultimately leading to potent and long-lasting antigen-specific humoral and cellular immune responses. Moreover, in principle, any eukaryotic sequence could be encoded by self-amplifying mRNA without the need to change the manufacturing process, thereby enabling a much faster and flexible research and development timeline than the current vaccines and hence a quicker response to emerging infectious diseases. This chapter highlights the rapid progress made in using non-virally delivered self-amplifying mRNA-based vaccines against infectious diseases in animal models. We provide an overview of the unique attributes of this vaccine approach, summarize the growing body of work defining its mechanism of action, discuss the current challenges and latest advances, and highlight perspectives about the future of this promising technology.

A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies

“…Most importantly, a correct balance between saRNA-mediated protein expression and adequate immune stimulation will be needed for the best vaccine outcome. Currently, scientists are trying to improve saRNA delivery systems by introducing on/off synthetic RNA circuits, which might allow for controlled expression of immunomodulators [ 85 ]. Another approach is the introduction of trans-amplifying mRNAs; in this modality, the saRNA is divided into two transcripts, thus reducing the sizes of individual saRNAs (Fig.…”

Self-Amplifying RNA Approach for Protein Replacement Therapy

“…This averts any possible intervention in the human genome and makes it a safe and feasible strategy [ 26 ]. On the other hand, saRNA provides advancement for protein replacement [ 27 ]. The main differences between conventional mRNA and saRNA vaccine technologies are as follows: in case of saRNA, a lower dose of vaccine is required compared with the conventional mRNA-based immunization strategy.…”

An Update on mRNA-Based Viral Vaccines

“…The development of mRNA-based vaccines against infectious diseases has been previously summarized in self amplifying and conventional non-replicating RNA technologies [112,124,125]. This section reviews recent updates on preclinical and clinical studies on mRNA vaccines against other viruses, including human respiratory syncytial virus (RSV), Zika virus, rabies, and human immunodeficiency virus (HIV).…”