Development and utilization of mRNA-based vaccine, mechanism behind mRNA vaccine

Author: Durga Naik

Development and utilization of mRNA-based vaccine

Introduction:

The COVID-19 pandemic has significantly increased public interest in mRNA vaccinations. MRNA 1273(Moderna) & BNT 162 (Pfizer-BioNTech ) both the vaccine is based on mRNA technology. The latest round of immunization techniques marks a substantial shift from traditional strategies. mRNA-based vaccines, such as the COVID-19 vaccine created by Pfizer-BioNTech and Moderna, work by telling cells in the body to manufacture a protein typical of the virus, thus inducing an immune response. DNA-based vaccinations work similarly, using DNA rather than mRNA to instruct the immune system to identify and combat the virus. Viral vectors are an alternative strategy in which the genetic material of the target virus is delivered into cells via a harmless virus, thereby inducing an immunological response. A viral vector, for instance, is used in the Johnson & Johnson COVID-19 vaccination employs an adenovirus vector. Finally, to induce a strong immune response, antigen-presenting cells (APCs) are injected into the body after being removed from the body and exposed to viral components in a laboratory. The effectiveness, scalability, and safety profiles of each of these approaches present exciting new directions for the development of vaccines, with the potential to completely transform the industry.

– BNT162b2 (Comirnaty): Developed by BioNTech (Germany) and Pfizer (USA).

– mRNA-1273 COVID-19: Developed in Cambridge, MA, USA.

The mRNA-based vaccination Comirnaty, created by Pfizer and BioNTech, is the first to get emergency authorization from the FDA on December 11, 2020, and from the EMA on December 21, 2020. The FDA approved Moderna’s vaccine shortly after on December 18, 2020, and the EMA authorized it on January 6, 2021.

Mechanism:

A single-strand mRNA coding for the SARS-CoV-2 spike proteins is present in both vaccinations. This particular protein is present on the surface of the virus and is known to facilitate the coronavirus’s entry into host cells. The 5′ cap, UTR sections preceding and following the actual coding sequence, and a poly(A) tail at the 3′ end of the single strand comprise the mRNA itself. These structures support translation and give the molecule stability in the cytoplasm. Moreover, the two vaccines are nucleoside-modified, which means that codons encoding the same amino acid have been created by exchanging a few single RNA nucleotides, matching tRNA molecule is present in higher concentrations throughout the cell. On the other hand, because the relevant tRNA molecule is present in higher concentrations within the cell, these new codons translate more efficiently. Lipid nanoparticles (LNPs), which encase the mRNA, are a crucial additional ingredient in the vaccinations. In terms of the mRNA transport in vivo, LNPs serve two purposes: first, they shield the nucleic acid from RNAses’ degradation in the extracellular space, and second, they facilitate the mRNA’s absorption into the cells at the injection site. The two vaccinations approved by the FDA and EMA are structurally different, despite their remarkable similarity in terms of lipid type for the lipid nanoparticles.

Once the mRNA has been released in the cytoplasm of the target cell, it will pass through the process of translation, creating the SARS-CoV-2 spike protein’s peptide chain that will be properly folded in further steps. The mRNA strand itself is broken down after translation. Body cells display antigens on special cell receptors (MHC) on the cell surface, where they can be recognized by human immune cells. This generates a humoral and cell-mediated immune response by activating different types of antigen-specific lymphocytes (B and T cells). B-cells produce high amounts of antibodies that can bind the epitopes of the vaccinated antigen in order to neutralize it, whereas cytotoxic T-cells specifically kill body cells presenting the antigen on their MHC receptors. The remaining antibodies and immune cells continue to circulate through the body. They are the basis for immunity against SARS-CoV-2.

In the case of a secondary infection, the virus can quickly be recognized and is neutralized at the epitopes of its spike protein by antibodies. At the same time, cytotoxic T-cells specifically spot infected body cells and kill them to prevent the spreading of the SARS-CoV-2 infection inside the body.

Doses:

Both vaccines – BNT162b2 and mRNA-1273 – are administered two times. The second injection of the vaccine should mimic a secondary infection by inducing new production of the antigen and serves as a booster to obtain a greater immunity against SARS-CoV-2. According to the vaccination schedule the second dose of BNT162b2 is given after 21 days, whereas mRNA-1273 is readministered after 28 days. The two vaccines also differ as BNT162b2 has to be diluted prior to use virus is destroyed and the onset of COVID-19 disease symptoms can be prevented.

Efficacy and Safety:

 It has been demonstrated that both vaccines are very effective. The results of both tests show that the age, gender, ethnicity, or pre-existing medical conditions have no effect on the vaccines’ effectiveness. Compared to the traditional method of injecting the antigen alone, mRNA vaccines may offer a stronger form of immunity because they activate specific killer cells in addition to generating antibodies as part of a humoral immune response.

The vaccination itself is not contagious because it is based on mRNA, thus worries about a genetic fragment being inserted into our DNA genome are baseless. Additionally, because it is broken down by enzymes upon translation, mRNA only has a brief half-life in the cytoplasm. Despite this, unexpected immunological reactions to the mRNA strand can still result in negative effects, particularly when different species react differently to the same material.

In clinical trials, the mRNA vaccines approved by the FDA and EMA have often demonstrated mild to moderate side effects that resolve a few days after immunization. These side effects, which are more prevalent in younger people and occur after the second dose, include injection site soreness, exhaustion, headaches, and pain in the muscles and joints, all of which are indicative of an immunological reaction. However, because mRNA vaccinations are relatively new, long-term consequences and immunization durability remain unknown, requiring continued surveillance. Furthermore, it’s yet unknown if those who have received vaccinations might spread the virus without showing any symptoms. Moreover, there is a dearth of study on possible adverse effects for expectant mothers. To fully comprehend the effects and safety of mRNA vaccines in various populations, more research is necessary.

Time spent in production and standardization:

Unlike certain conventional vaccines, the vaccine only contains the building instructions for the infectious portion of the virus, not the infectious portions themselves. As a result, time can be saved during the virus’s development, multiplication, inactivation, and isolation of the desired portion. The tissue that the viruses are produced on-chicken or mammalian eggs is another resource that is extensively consumed in this conventional method. On the other hand, the mRNA-based vaccine is readily replicable in biomedical laboratories worldwide once the genetic sequence of the antigen is known. Because labs typically have the necessary supplies, producing mRNA vaccines is therefore less expensive and time-consuming. Additionally, this makes it easier to produce vaccines on a big scale, which is crucial for lessening the effects of pandemics.

Storage:

The distribution of mRNA-based vaccinations to the public is hampered by the requirement that they be carried and maintained at extremely low temperatures. For instance, Moderna vaccination may withstand slightly higher temperatures (-25°C to -15°C), but Comirnaty must be stored between -90°C and -60°C. The Moderna vaccine lasts seven months, whereas the Comirnaty vaccine is only good for six months. Therefore, in order to guarantee that the vaccines manufactured can really reach their beneficiaries, vaccine distribution needs to be logistically well-organized. There isn’t much time left for ingestion once the vials are opened. Flexibility However, one major benefit of mRNA vaccines over traditional immunization techniques is the ability to model the mRNA and alter its internal mechanisms of the organisms.

Age indication: Comiranty-16 years old and older and Moderna- 18 years old and older

Dosage: Comiranty-30 micrograms of COVID-19 mRNA Vaccine (embedded in lipid nanoparticles) and Moderna-100 micrograms of messenger RNA (mRNA) (embedded in SM-102 lipid nanoparticles).

Administration: Intramuscularly.

Booster Immunogenicity:

Between the ages of 18 and 55 who had finished a 2-dose primary series of Comirnaty about six months earlier and had no signs of a previous SARS-CoV-2 infection were administered a booster dose in an unpublished longitudinal immunogenicity study (summarized in the FDA Fact Sheet).

Booster Efficacy:

Beginning 12 days after administration, individuals who received a booster dose had significantly lower rates of SARS-CoV-2 infection (by 11.3-fold) and severe COVID-19 (by 19.5-fold) compared to those who did not receive a booster dose.

Adverse effects:

Pain at the injection site pain, fatigue, headache, myalgia and chills, arthralgia, pyrexia and injection site swelling, nausea/vomiting, axillary swelling/tenderness, fever, redness.

Vials:

Comirnaty- 2 mL clear multidose vial. Each vial contains 5 doses of 0,3mL. Pack size: 195 vials.

Moderna-5 ml dispersion in a vial. Each vial contains 10 doses of 0.5mL. Pack size: 10 multidose vials.

Exclusion criteria:

Pregnant and nursing women are frequently excluded from vaccine studies because they are not regarded as a high priority group.

Conclusion:

Comirnaty, the first vaccines licensed for human use, effectively treated COVID-19 and was based on modified non-replicating mRNA lipophilic nanoparticle (mRNA-LNP) technology. They are used extensively everywhere in the world. The stability issues with medicines are a major disadvantage of these vaccinations. Medication must be handled, stored, and transported carefully before being administered to patients. Improper handling might reduce the medication’s potency. This study compared the in-use stability of clinical samples obtained from Moderna and Comirnaty. The results demonstrate that, under different handling and stress conditions, the two vaccines display extremely different particle size profiles and behaviours, even though they share the same mRNA-LNP technology.

Reference:

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