The Current Landscape of mRNA Vaccines Against Viruses and Cancer-A Mini Review

Abstract

Both infectious viral diseases and cancer have historically been some of the most common causes of death worldwide. The COVID-19 pandemic is a decidedly relevant example of the former. Despite progress having been made over past decades, new and improved techniques are still needed to address the limitations faced by current treatment standards, with mRNA-based therapy emerging as a promising solution. Highly flexible, scalable and cost-effective, mRNA therapy is proving to be a compelling vaccine platform against viruses. Likewise, mRNA vaccines show similar promise against cancer as a platform capable of encoding multiple antigens for a diverse array of cancers, including those that are patient specific as a novel form of personalized medicine. In this review, the molecular mechanisms, biotechnological aspects, and clinical developments of mRNA vaccines against viral infections and cancer are discussed to provide an informative update on the current state of mRNA therapy research.

Keywords: cancer vaccination; clinical trials of mRNA vaccines; mRNA modifications; mRNA vaccine delivery; mRNA vaccine developers; mRNA vaccine mechanism; viral vaccination.

Figure 1

Viral and Cancer RNA vaccine mechanism. (1) The viral Ag, TAA or TSA-encoding mRNA enters the APC and then the cytosol following endosomal escape. (2) The mRNA is translated by the host ribosomal machinery into the encoded Ag, which is then either (3A) degraded by the proteasome and enters the endogenous MHC I pathway; (3B) exocytosed from the APC via the secretory pathway; or (3C) enters the autophagic pathway and is internalized by an autophagosome. (4A) Proteasome-mediated degradation yields fragments (blue), including the epitope (yellow). Following secretion, the Ag either (4B) enters an APC via endocytosis and then the exogenous MHC II pathway; or (4C) the native antigen will circulate through the lymphatic system to secondary lymphoid organs. (5A) The epitope binds MHC I at the rough endoplasmic reticulum (RER) and traffics to the cell membrane for surface presentation via the secretory pathway. (5B) The Ag, internalized via endocytosis or processed by autophagy, is digested into fragments, including the epitope (red), via lysosome-mediated degradation. (6) The epitope binds MHC II and displaces class-II associated invariant chain peptide (CLIP), and the complex then traffics to the membrane for surface presentation. (7) The APCs migrate to secondary lymphoid organs, including the lymph node. The APCs present the epitope-loaded MHC I and MHC II complexes to activate naive CD8 and CD4 T cells, respectively, and follicular DCs and subcapsular sinus (SCS) macrophages present the native Ag to activate naive B cells, driving plasma cell differentiation and Ab production. This figure was created with BioRender.com.