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2020-12-31| COVID-19In-Depth

Pick your Potion, An Overview of the COVID Vaccines

by Eduardo Longoria
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With record timing and pushing through precedents in the fields of biomanufacturing and immunology, many private enterprises have come out with vaccines for the Coronavirus. As a result of this pandemic, the FDA in the US granted its first approval for an mRNA vaccine. The world is making decisions as to which vaccine they will stake their citizen’s health on.

Despite all the advancements in technology. The idea is still very similar. The original vaccines were simply a deactivated version of the whole virus being exposed to the patient as a means of stimulating their immune system. Now, with advances in biomanufacturing, people can produce instructions (mRNA) to encourage human cells to produce viral proteins, produce viral proteins in vitro or even get an unrelated virus to deliver instructions to the immune system.

While there are a variety of reasons that nations and individuals choose one over the other. We have summarized an overview including the pros and cons of those major vaccines on their efficacy rather than their political implications. This will explain each category of vaccines and how they are made as well as their efficacy in clinical trials.

 

mRNA

mRNA is known as Messenger RNA and is able to deliver instructions to the ribosomes of the body’s cells and get them to produce a specific protein. In the case of coronavirus vaccines, these mRNA instructions are used to produce the spike protein from the coronavirus until the mRNA is eventually disposed of by the cell. Then this protein induces an immune system response in the same way as being exposed to the virus would.

Pfizer-BioNTech’s was the first coronavirus vaccine (BNT162b2) to be approved in the US and has the distinct advantage of being able to be administered to 16-year-olds as opposed to adults. The side effect profile, especially after the second dose, also appears to be milder for BNT162b2 compared to mRNA-1273.

Moderna’s vaccine (mRNA-1273) was approved by the US FDA in mid-December under an Emergency Use Authorization. Moderna’s vaccine has easier storage requirements (shipped at -20 °C /- 4 °F and kept stable for 30 days at the temperature of a home refrigerator) when compared to the Pfizer-BioNTech’s as well as better protection from severe COVID-19. Of the 196 COVID-19 cases in the clinical trial, none of the participants who got mRNA-1273 developed severe COVID-19, while 30 of the cases in the placebo group were classified as severe.

Despite concerns from the public, mRNA vaccines cannot give someone coronavirus as they do not carry all of the nucleic acid instructions for the whole virus and also do not have the means by which to insert themselves into the nucleus of a human cell.

 

Whole Virus

The CoronaVac vaccine has been described as old-fashioned due to the vaccine’s mechanism of action. The method of production and mechanism of action are updated versions of the original vaccines produced by simply making a deactivated version of the virus to expose the patient to. The vaccine uses alum as an adjuvant (immuno-stimulant compound to increase vaccine efficacy) and the virus is deactivated using beta-propiolactone (4 member ring chemical). This kind of vaccine has a long history of efficacy and ease of manufacturing but in phase 2 clinical trials were only tested on healthy adults aged 18-59 and so will likely require more testing before use in at-risk groups. The vaccine is produced by a Chinese firm, SinoVac.

 

Viral Vector

Viral vector vaccines have the benefit of making use of a known and well-studied virus (usually an adenovirus) to transport and enable the vaccine to work. The vaccine works by disabling the viral vector’s ability to reproduce but allows it to be able to get into a human cell and introduce its genetic material. As part of the vaccine, the researcher will insert a section of either RNA or DNA into the genetic code of the virus. This RNA or DNA is often intended to induce the human cell to produce a viral protein (most often the spike) that will trigger an immune system response.

The AstraZeneca/Oxford vaccine makes use of a modified chimpanzee adenovirus (ChAdOx1) with coded SARS-CoV-2 proteins to encourage human cells to produce the spike protein commonly found on the surface of the coronavirus.

An advantage of using a viral vector as opposed to mRNA is its durability. The adenovirus makes use of DNA as opposed to RNA and so benefits from the increased stability of that molecule. This increased stability makes storage for 6 months in a standard 2-8 °C refrigerator feasible.

Gam-COVID-Vac, conventionally known as “Sputnik V” is a vaccine developed by the Gamaleya research institute in coordination with the Russian ministry of defense. The vaccine is expected to provide immunity from SARS-CoV-2, the virus that causes COVID-19, for up to two years with two doses consisting of two serotypes (variation within a species of the virus) of human adenovirus. Each serotype carries an S-antigen of SARS-CoV-2, which enters human cells and produces an immune response. It is a viral vector vaccine that employs adenovirus 5 to carry the DNA encoding of the needed immune response into cells.

The Janssen vaccine (JNJ-78436735) is produced by Janssen pharmaceuticals, a branch of Johnson and Johnson. The vaccine is called Ad.26.COV2.S and is a recombinant vector vaccine that uses a human adenovirus (Ad26) to express the SARS-CoV-2 spike protein in cells. The vaccine, because of the adenovirus, is predicted to remain stable for two years at -20 °C and at least three months at 2–8 °C. This increased stability will be a huge factor in making it available to rural areas and countries with poorly developed transportation infrastructure.

 

Protein

Maryland-based biotechnology company Novavax specializes in “protein subunit” vaccines. They make their vaccine by using virus-like nanoparticles as a base and cover them with genetically engineered pieces of the coronavirus spike protein.

Novavax uses an insect virus called a baculovirus to get the coronavirus spike protein into moth cells, which then produce the protein. This is harvested and mixed with an adjuvant (immune booster) based on saponin, found in soap bark trees.

Sanofi and GlaxoSmithKline in collaboration make use of the baculovirus to grow units of spike protein to create their vaccine. Sanofi contributes its recombinant S-protein COVID-19 antigen and GSK will contribute its proven pandemic adjuvant technology (ingredient added to enhance the immune response, and which may reduce the amount of vaccine protein required per dose).

Protein subunit-based vaccines have the advantage of being more direct as regards stimulating the immune system. The proteins that are attached to the virus-like nanoparticles are directly introduced to the patient’s body, rather than introducing mRNA or other nucleic acid meant to induce their production in the body.

Of all of these vaccines, the ones that will likely be available to Americans in the coming year are those produced by J&J, AstraZeneca (already available to the elderly), Pfizer/BioNTech, Moderna (already available to the elderly), and Novavax. Currently, not a single one of these companies is able to produce sufficient vaccines to keep up with the demands of the whole US and so likely most Americans will have more limited choices than being able to choose from any of these five companies.

While there are many other factors that go into both individual and national decisions regarding vaccine dosage. We here at GeneOnline hope that this article has been informative and will aid the process of deciding on a scientific basis.

References

1. Moderna Gains FDA Authorization for Its Coronavirus Vaccine | The Motley Fool
2. Understanding mRNA COVID-19 Vaccines | CDC
3. Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial | medRxiv
4. How the Oxford-AstraZeneca Covid-19 Vaccine Works – The New York Times (nytimes.com)
5. Large Phase III Trial Launched for J&J’s COVID-19 Vaccine (clinicalomics.com)
6. Covid-19 vaccine: When can YOU get it? It depends on your health, occupation and where you live – CNN
7. Novavax begins 3rd-stage clinical trial in U.S. for COVID-19 vaccine – UPI.com
8. NVX-CoV2373 SARS-CoV-2 Vaccine — Precision Vaccinations

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