What are mRNA vaccines?

mRNA vaccines are a type of nucleic acid vaccine. Though mRNA was first discovered in 1961, vaccines based on mRNA are truly a product of the 21st century.

Here’s a step-by-step look at how mRNA vaccines are made:

• Scientists first study the pathogen they want to target. This study includes understanding the structure, genome and working of the pathogen. For example, in the case of SARS-CoV-2 (which causes COVID-19), scientists discovered early on that spike (S) proteins on the coronavirus are crucial to how the virus gains entry into healthy human cells. After this, scientists started looking for ways to use or block this S protein for therapeutic purposes.
• Once the scientists know which protein they want to use, they design and make the corresponding mRNA sequence for it. This sequence is basically a set of instructions that will tell the body’s cells how to make the desired antigen protein.
• The mRNA sequence is then introduced into the cells in an appropriate format and through the appropriate modality to improve results. Some of the formats for mRNA therapeutics include: “encapsulation by delivery carriers, such as lipid nanoparticles, polymers, peptides, free mRNA in solution, and ex vivo through dendritic cells”. The vaccine may be given into the skin (intradermally), under the skin (subcutaneous), into a muscle (intramuscular), into a vein (intravenously) or into a lymph node (intranodal). Less commonly, the vaccine may be delivered through an intranasal injection (through the nose), intravaginal injection (into the vagina) or intratumoral injection (into a tumour).
• Once inside the cells, the mRNA instructs the ribosomes to make the intended protein and ideally hone the body’s immune response to fight off the pathogen.

At least two mRNA have emerged as promising COVID-19 vaccine candidates in human trials: Pfizer and BioNTech’s BNT162b2 vaccine and US-based Moderna, Inc.’s mRNA-1273 vaccine candidate against COVID-19, which has shown promising results in interim analyses based on phase 2 of human trials:

1. Moderna COVID-19 vaccine candidate: mRNA-1273
2. Pfizer and BioNTech COVID-19 vaccine candidate: BNT162b2

At its heart, the mRNA vaccine technology is about designing and creating mRNA that—when introduced into the body—can induce the cells to produce certain antigen proteins. As these proteins mimic a part of the pathogen (disease-causing microbe), our immune system mounts a response to it.

To do this, scientists need to first figure out the structure as well as the genome of the pathogen. This helps them to clearly identify which part of the pathogen they can use to safely yet effectively induce an immune response. (In the case of the COVID-19 causing virus SARS-CoV-2, the genome sequence was cracked in January 2020—within weeks of the world finding out about this new viral infection.)

Now, we know that the job of vaccines is to train the body to recognise a pathogen and build an appropriate response to it in a way that is much safer than actually contracting a disease and then developing immunity (sometimes lifelong immunity) to it.

Research is on to look for an effective mRNA vaccine for influenza, rabies and Zika virus infection. Additionally, medical researchers have explained that gene-based mRNA vaccines may have some benefits over protein-based vaccines and vector vaccines.

Gene-based vaccines are those that contain instructions for the body to make an immune response-inducing protein.

Protein-based vaccines already contain a part of the antigen (subunit vaccine) or a weakened or attenuated antigen protein (examples include the polio vaccine).

Vector-based vaccines use a self-limiting or harmless pathogen as a carrier or vector to deliver the vaccine—the vaccine itself could be gene-based. An example of this is ChAdOx-1 nCov-19, the COVID-19 vaccine candidate by Oxford University and AstraZeneca AZD1222, which uses an adenovirus that infects chimpanzees as a vector.

Here are some of the key advantages of mRNA vaccines:

• Gene-based vaccines recruit CD8+ cytotoxic T cells (killer T cells) in addition to antibodies and CD4+ helper T cells, because they can trigger the pathways in the right way.
• The efficacy of vector-based vaccines can be reduced if the body is already immune to the carrier microbe. Just gene-based vaccines that don’t run this risk.
• In the future, scientists may be able to make mRNA vaccines that are thermostable, meaning they won’t have to be frozen during transport and storage.

The US government has reportedly bought “hundreds of millions of doses of ChAdOx1 nCoV-19, mRNA-1273, BNT162b2, and an investigational non–replicating viral vector vaccine in early trials from Johnson & Johnson–owned Janssen Pharmaceutical Companies, as well as other candidates” under Operation Warp Speed.

Though mRNA vaccines have been around since the 1990s, it was only in the 2000s that scientists were able to reduce their side-effects enough to consider them fit for human trials. Potential side-effects of successful mRNA vaccines may include:

• Fever
• Headache
• Body ache
• Exhaustion for a short period of time