So What is an mRNA Vaccine?

An explainer on the novel vaccine technology used against the novel coronavirus

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When Edward Jenner demonstrated immunity against smallpox by inoculating a 13-year-old boy with cowpox virus in 1796, the era of vaccination began. This first vaccine used live virus strain to induce active immunity. Killed organisms (bacteria and virus), chemical-treated toxoids, and bacterial and viral structural components made up of protein and carbohydrate have since been used to prepare vaccines against more than twenty-five bacteria and viruses.

The vaccines currently leading the pack against the novel coronavirus, however, use neither of the above methods. Both the vaccines, developed by Moderna and Pfizer, are produced via a novel technology that uses mRNA of the virus rather than killed virus particles or a structural component of it. If approved, these will be the first mRNA-based vaccines ever. To understand how does an mRNA vaccine works and how it is different than the existing platforms, a quick look at the conventional vaccine technologies would be pertinent.

The Old Way

To produce a vaccine against the novel coronavirus using conventional methods, one of the following approaches can be adopted:

  • Whole virus vaccine (either inactivated/killed or live-attenuated): Inactivating the virus (using formaldehyde, for example) so that it retains the ability to induce immunity in the body when injected but is too weakened to cause infection, is a classic way to produce vaccines.
  • Subviral particle vaccine uses a part(s) of the virus instead of the whole virus. Protein, and sometimes carbohydrate, structural components that act as antigens are commonly employed. In case of SARS-CoV-2, the spike protein (S protein) is a strong candidate to be used as a vaccine constituent. Preparations of the virus particle induce the production of antibodies in the host and lead to immunity for a variable amount of time.

The New Way — mRNA

mRNA-based vaccine technology has been around for more than a decade but there are no approved vaccines — yet — produced using it. The need for a new platform was felt to overcome various problems with the existing technologies. For example, vaccines using live-attenuated viruses carry the risk (small but non-negligible) of causing the infection if used in immunocompromised individuals. The development of conventional vaccines is a long and tedious process, taking on average 6 to 10 years. This is in part due to the fact that each vaccine has to be built from scratch. Finally, some vaccines, especially sub-particle vaccines, may not induce an optimum immune response as they fail to excite both arms of the immune system(antibodies and T-cells).

mRNA promises to solve some of these problems as we discuss towards the end.

Nucleic acid, mostly in the form of DNA but RNA is some viruses, is the blueprint that codes for all the proteins produced in living organisms — both structural and functional protein. A gene is a DNA sequence that codes for a specific protein. In the process of protein synthesis, DNA (or nuclear RNA in the case of certain viruses) is first transcribed into messenger RNA (mRNA). mRNA carries the exact code as that of the gene DNA. mRNA comes out of the nucleus and the protein synthesis machinery of the cell — comprising of ribosomes and endoplasmic reticulum — translates it into amino acid chains, one or more of which combine to form a protein.

mRNA vaccines only contain an RNA sequence— there are no killed/inactivated viruses, proteins, or viral carriers. Upon injection, the mRNA uses the host cells to produce the protein antigen it is encoding.

The vaccine produced by Moderna, named mRNA-1273, contains an RNA sequence that codes for the S-glycoprotein of the SARS-CoV-2 virus. This spike protein is responsible for the entry of the virus into the host (human) cells. The mRNA in question is packaged into a lipid nanoparticle capsule, which makes for an efficient delivery system. When injected into the body, the mRNA uses the host’s protein synthesis machinery to produce S- glycoprotein, which triggers both the humoral (antibodies, B-cells) and cellular (T-cells) arms of the immune system.

The mRNA Promise

A highlighted benefit of mRNA-based vaccine technology is the rapidity and ease of the development process. By bypassing the need for tedious purification of virus particles or sub-particles, the development of an mRNA vaccine is expected to be, at least in theory, significantly faster. The approach is easily scalable too. Once an RNA sequence is finalized, copying it over millions of times is a matter of weeks. Another advantage of the platform is its re-usability. Theoretically, the technology developed for one mRNA vaccine can be used, with little modification, to prepare other vaccines as well.

On the clinical front, the initial response data and safety profile for both the vaccines currently in trials are encouraging. How these vaccines — and the mRNA vaccine paradigm as a whole — compares to the conventional modes of vaccine development in terms of efficacy and safety, however, is yet to be seen and will require time.

Physician by profession and nerd by choice. I read & write about science, medicine, technology & programming.

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