Messenger RNA-based vaccines: Past, present, and future directions in the context of the COVID-19 pandemic

Abstract

mRNA vaccines have received major attention in the fight against COVID-19. Formulations from companies such as Moderna and BioNTech/Pfizer have allowed us to slowly ease the social distancing measures, mask requirements, and lockdowns that have been prevalent since early 2020. This past year's focused work on mRNA vaccines has catapulted this technology to the forefront of public awareness and additional research pursuits, thus leading to new potential for bionanotechnology principles to help drive further innovation using mRNA. In addition to alleviating the burden of COVID-19, mRNA vaccines could potentially provide long-term solutions all over the world for diseases ranging from influenza to AIDS. Herein, we provide a brief commentary based on the history and development of mRNA vaccines in the context of the COVID-19 pandemic. Furthermore, we address current research using the technology and future directions of mRNA vaccine research.

Keywords: Drug delivery; Immunology; Nanotechnology; SARS-CoV2; Vaccines; mRNA.

Graphical abstract

Fig. 1

Daily laboratory-confirmed SARS-CoV-2 infections in Israel (Nov 1, 2020, to April 3, 2021). Reproduced with permission from Haas et al. 2021 .

Fig. 2

mRNA and saRNA protein production in antigen presenting cells. Reproduced without changes from Sandbrink and Shattock, 2020 . GOI: Gene of interest; UTR: Untranslated regions; nsPs: non-structural proteins; CTL: cytotoxic T lymphocyte.

Fig. 3

Mechanism by which mRNA vaccines elicit immunity. The mRNA encoding the viral protein enters the cell where it is translated into protein by the ribosome. The resulting protein is broken down into peptides by the proteasome or transported by the Golgi apparatus to the outside of the cell. The remaining fragments in the cell are presented as a complex. Additionally, protein outside of the cell can be taken up by various immune cells and fragmented into smaller pieces by the endosome. Figure created using BioRender.com.

Fig. 4

Cellular mechanism of immune activation. Reproduced from Ghaffari et al., 2020. (1) The SARS-CoV-2 virus enters the host cell via interaction between viral spike and host angiotensin-converting enzyme 2 (ACE2) proteins. (2,3) Following replication and release from the host cells, a subset of viruses will be engulfed and digested by antigen-presenting cells (APCs) like macrophages or dendritic cells. (4) Fragmented SARS-CoV-2 antigen(s) will be presented to T helper cells, which in turn will interact and activate B cells. (5) Activated B cells will proliferate and differentiate into plasma or memory B cells with high-affinity binding receptors for the original SARS-CoV-2 antigen. Plasma cells secrete their SARS-CoV-2-specific receptors in the form of IgM, IgG, or IgA antibodies. (6) Antibody-mediated neutralization occurs when SARS-CoV-2-specific antibodies bind to viral antigen(s) and prevent virus interaction and entry into host cells.

Fig. 5

Advantages of oral vaccine delivery. Advantages include the lack of a need for painful intramuscular injections and decreased generation of biohazardous plastic material by utilizing the body’s existing gastroenteric mechanisms. Figure created using BioRender.com.