Updated Considerations for the Immunopharmacological Aspects of the “Talented mRNA Vaccines”

Abstract

Messenger RNA (mRNA) vaccines belong to a new class of medications, RNA therapeutics, including both coding and non-coding RNAs. The use of mRNA as a therapy is based on the biological role of mRNA itself, namely its translation into a functional protein. The goal of mRNA vaccines is to produce a specific antigen in cells to elicit an immune response that might be prophylactic or therapeutic. The potential of mRNA as vaccine has been envisaged for years but its efficacy has been clearly demonstrated with the approval of COVID-19 vaccines in 2021. Since then, mRNA vaccines have been in the pipeline for diseases that are still untreatable. There are many advantages of mRNA vaccines over traditional vaccines, including easy and cost-effective production, high safety, and high-level antigen expression. However, the nature of mRNA itself and some technical issues pose challenges associated with the vaccines’ development and use. Here we review the immunological and pharmacological features of mRNA vaccines by discussing their pharmacokinetics, mechanisms of action, and safety, with a particular attention on the advantages and challenges related to their administration. Furthermore, we present an overview of the areas of application and the clinical trials that utilize a mRNA vaccine as a treatment.

The Platform Technology Approach to mRNA Product Development and Regulation

“… Rare or metabolic diseases -methylmalonic acidemia, ornithine transcarbamylase deficiency, phenylketonuria, propionic aciduria, primary ciliary dyskinesia An analysis of data in clinicaltrials.gov as of 1 April 2023 [12] found there were 416 trials involving mRNA products, of which 20% involved diseases other than SARS-CoV-2. The diseases were as above but with trials for breast cancer, glioblastoma, hepatitis B and tuberculosis were also identified.…”

“…This is because for most vaccines which are administered intramuscularly, most of the dose remains in the muscle and the rest is eliminated through the lymphatic system. To date regulators have required some pharmacokinetic and biodistribution studies for mRNA-LNP products [12], especially ancestral COVID-19 vaccines, although human PK studies were not required. Specific analytical studies were required to be developed and validated, and preclinical methods that can be used for biodistribution studies have been reviewed [23].…”

Potential of DPD ((S)-4,5-dihydroxy-2,3-pentanedione) Analogs in Microparticulate Formulation as Vaccine Adjuvants

“…For instance, mRNA vaccines offer more benefits than traditional vaccines such as inexpensive production, easy scale-up, extended safety, and high-level antigen expression. There are still several unanswered questions about mRNA vaccines including challenges associated with the vaccines’ development and use [ 6 ]. There are several types of current vaccines, and their advantages and limitations are shown in Table 1 [ 7 , 8 ].…”

“…Traditional vaccines use weakened or inactivated pathogens as antigens that are heterogeneous and contain many epitopes. Some of these epitopes provide an extended T-cell response, but their contribution to immunogenicity is minuscule (6). For instance, mRNA vaccines offer more benefits than traditional vaccines such as inexpensive production, easy scale-up, extended safety, and high-level antigen expression.…”

Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus

“…These have, therefore, been framed here. Although not the focus of the review, we propose that the study of the shape of the viral genome and its function in processing viral RNAs may become key benchmarks for the development of RNA-based vaccines and antivirals [28,29]. Our system of cataloging the information we consider may be of great use in organizing the data on the interactions that other viruses have among other hosts in the future.…”