Abstract
Increases in the world’s population and population density promote the spread of emerging pathogens. Vaccines are the most cost-effective means of preventing this spread. Traditional methods used to identify and produce new vaccines are not adequate, in most instances, to ensure global protection. New technologies are urgently needed to expedite large scale vaccine development. mRNA-based vaccines promise to meet this need. mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they (1) involve neither infectious elements nor a risk of stable integration into the host cell genome; (2) generate humoral and cell-mediated immunity; (3) are well-tolerated by healthy individuals; and (4) are less expensive and produced more rapidly by processes that are readily standardized and scaled-up, improving responsiveness to large emerging outbreaks. Multiple mRNA vaccine platforms have demonstrated efficacy in preventing infectious diseases and treating several types of cancers in humans as well as animal models. This review describes the factors that contribute to maximizing the production of effective mRNA vaccine transcripts and delivery systems, and the clinical applications are discussed in detail.
Highlights
Increases in the world’s population, population density, global travel, and contact between people promotes the spread of emerging pathogens.Zoonosis represents a constant threat to introduce previously uncharacterized pathogens, such as HIV, SARS, MERS CoV, and SARS-CoV-2, into the population [1,2]
The results protamine in a phase 1 clinical trial were suboptimal, though were much improved in preachieved by vaccination with mRNA encoding rabies virus glycoprotein (RABV-G) comclinical studies by adopting a lipid-containing nanoparticle (LNP) delivery system [49]
The majority of early work with mRNA vaccines has focused on cancer
Summary
Increases in the world’s population (approaching 7.8 billion), population density, global travel, and contact between people promotes the spread of emerging pathogens. Self-replicating constructs include unrelated antigenic proteins (i.e., the RDRP complex) capable of inducing a strong immune response that suppresses translation and immunogen production. Double-stranded RNA intermediates formed during self-replication are the natural ligands of cytoplasmic RNA sensors RIG-I and melanoma differentiation-associated protein 5 (MDA5) Ligation by these receptors initiates the release of type I interferons (INFα/β) and activation of the interferon response gene cascade and innate immunity [25]. Exogenous circRNAs avoid recognition by cellular RNA sensors (i.e., RIG-I) and TLR without nucleoside modification, thereby abrogating innate immune responses in animal models as well as cultured TLR-expressing cells These finding suggest that circRNA vaccine constructs could provide an alternate, improved approach to RNA-based vaccination. The potential use of circRNA-based vaccines in cancer stem cell therapy has been proposed [32]
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