Clinical and immunological effects of mRNA vaccines in malignant diseases

Abstract

In vitro-transcribed messenger RNA-based therapeutics represent a relatively novel and highly efficient class of drugs. Several recently published studies emphasize the potential efficacy of mRNA vaccines in treating different types of malignant and infectious diseases where conventional vaccine strategies and platforms fail to elicit protective immune responses. mRNA vaccines have lately raised high interest as potent vaccines against SARS-CoV2. Direct application of mRNA or its electroporation into dendritic cells was shown to induce polyclonal CD4+ and CD8+ mediated antigen-specific T cell responses as well as the production of protective antibodies with the ability to eliminate transformed or infected cells. More importantly, the vaccine composition may include two or more mRNAs coding for different proteins or long peptides. This enables the induction of polyclonal immune responses against a broad variety of epitopes within the encoded antigens that are presented on various MHC complexes, thus avoiding the restriction to a certain HLA molecule or possible immune escape due to antigen-loss. The development and design of mRNA therapies was recently boosted by several critical innovations including the development of technologies for the production and delivery of high quality and stable mRNA. Several technical obstacles such as stability, delivery and immunogenicity were addressed in the past and gradually solved in the recent years.This review will summarize the most recent technological developments and application of mRNA vaccines in clinical trials and discusses the results, challenges and future directions with a special focus on the induced innate and adaptive immune responses.

SARS-CoV-2 mRNA Vaccines Elicit Different Responses in Immunologically Naïve and Pre-Immune Humans

“…Two proline mutations in the C-terminal S2 fusion machinery were inserted into the pre-fusion spike protein conformation to more closely mimic the intact virus (18)(19)(20). When displayed by antigen-presenting cells (APCs), the spike protein stimulates a similar immune response to antigens presented over the course of a natural infection (21). In human trials, both vaccines reported 95% efficacy in healthy adults in preventing symptomatic infection by SARS-CoV-2 (8,9).…”

Influenza Viruses: Innate Immunity and mRNA Vaccines

“…In addition, injection site (e.g., subcutaneous, intramuscular, intradermal, and intravenous) and mRNA vaccine delivery formulations (e.g. lipid nanoparticle) influence the potency of the immune response ( 21 ). For instance, lipid nanoparticle carrier systems further protect mRNAs from nuclease, and can target delivery to lymphatics and promote protein translation in lymph nodes by intramuscular injection ( 20 ).…”

Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2

“…LNPs in the two COVID-19 mRNA vaccines (i.e., Pfizer/BioNTech and Moderna) have a particular composition which makes their distribution in the body particular. LNPs usually contain four ingredients: cholesterol as a membrane fluidity modulator/stabilizer, phospholipids to form a lipid bilayer structure, a lipid-linked polyethylene glycol (PEG) that helps prolonging the half-life of the composition (ALC-0315 and SM-102 are the pegylated lipids added by Pfizer/BioNTech and Moderna, respectively [ 53 ]), and ionizable cationic lipids whose positive charges bind to the negatively charged backbone of mRNA, thus improving the release of mRNA from the endosome to the cytoplasm [ 54 ].…”