ABSTRACT
As the coronavirus pandemic rages across the globe, countless scientists are working towards manufacturing an effective vaccine against SARS- CoV-2, the viral pathogen that causes the disease. Could a relatively new type of vaccine, DNA vaccines, be the key?
This article discusses the action of vaccines on the immune system and elaborates on the process of making a DNA vaccine against Sars-CoV-2. It also summarizes the advantages of DNA vaccines over traditional vaccines, and concludes that a DNA vaccine would be ideal for the battle against COVID-19.
Image of SARS-CoV-2. (Courtesy Wikipedia)
INTRODUCTION
The human immune system identifies pathogens, disease-causing agents, based on the presence of certain proteins on their cell surface, which are known as antigens. This triggers the B-cells of the immune system into action, stimulating them to manufacture proteins called antibodies to combat pathogens. If the pathogen is one that the body has previously encountered, it is recognized by the immune system, and more antibodies are immediately produced. This is why you are less likely to get chickenpox if you have already had it once. Vaccines contain weakened strains of pathogens for the same reason: to elicit an immune response that will later help combat a serious infection, but not hazardous enough to cause a full-blown illness.
A traditional COVID-19 vaccine could eventually be developed, but the process would be a time-consuming one [1] .The weakened viruses, ones that aren’t strong enough to cause a full-blown infection, are grown in chicken eggs (or mammalian cells) and take months to form cultures[1]. Moreover, viruses such as the influenza virus mutate, changing the antigen proteins on their surface and making it harder to find a viable vaccine–a process that may take six months or more[1]. With the COVID-19 pandemic causing thousands of deaths daily, we simply do not have that kind of time on our hands.
DNA vaccines involve manipulating DNA(deoxyribonucleic acid), the molecule involved in heredity,to activate the necessary immune response[3].
HOW DO DNA VACCINES WORK?
The central dogma of molecular biology is the relationship between genes and proteins. DNA undergoes the process of transcription into mRNA, another type of nucleic acid, which is then translated into proteins. In short, the expression of genes leads to the manufacture of proteins. This also means that a change in the sequence of DNA changes the resultant protein formed.
In order for an antigen to activate the immune system, it must be expressed on the surface of a cell. An antigen is a protein and has a specific DNA sequence encoding it. But, viral DNA is not found in ordinary human cells. To transport the requisite DNA sequence into body cells, scientists often use a plasmid. A plasmid is an extrachromosomal, circular segment of DNA found in bacteria. A common principle of genetic engineering involves ‘cutting’ a plasmid, a process in which one can remove and add new bits of DNA . This is called Recombinant DNA Technology. Scientists used this method to manufacture insulin (a protein hormone vital for regulating glucose uptake in cells, malfunction of which could lead to diabetes mellitus.) in E. Coli bacteria. They input the DNA sequence that codes for insulin into a plasmid, insert it into bacteria, and produce insulin [5].
If we insert the DNA sequence that codes for antigen proteins into a plasmid, and insert the plasmid into an ordinary cell, the process of protein synthesis will soon take place, and antigen proteins will be produced on the surface of the cell [1]. This triggers the immune system, which immediately manufactures antibodies that remain circulating in the bloodstream until an actual infection arises. Cytotoxic T-cells will also be activated by the antigen proteins.
In fact, SARS-CoV-2 does have an antigen on its surface that would be an ideal target for a DNA vaccine: ‘ the spike protein’[4]. This protein binds to the human cell surface receptor ACE-2,angiotensin-converting enzyme, in order to enter the cell. A DNA vaccine targeting it would be effective, causing researchers to hope to use the spike protein in developing antibody treatments[4] .
Flowchart describing manufacture of DNA vaccines. Image courtesy Wikimedia Commons.
ADVANTAGES OF DNA VACCINES OVER ORDINARY VACCINES
DNA vaccines assure an effective immune response as antigens are produced within the body. Antibody levels are also as high as those released by ordinary vaccines, or better[1]. Moreover, they can be manufactured on a large scale for a lower cost than ordinary vaccines. They also take less time to produce; normal vaccines take years before they can even be tested. In that time, viruses could have undergone mutations, rendering a vaccine that was once thought effective as obsolete [1]. As DNA vaccines require only the specific DNA sequence encoding an antigen, they can be quickly manufactured in response to any mutations.
CONCLUSION
DNA vaccines have not yet been approved for use in humans, but successful immune responses have been obtained in animals, for pathogens like HIV and the Hepatitis -B virus[2]. The ongoing pandemic means that labs may be testing DNA vaccines sooner than was previously thought. The technology may still require perfection, but for now, it’s our best hope.
REFERENCES:
[1]Schmidt, C. \”Genetic engineering could make a COVID-19 vaccine in months rather than years.\” Scientific American. https://www.scientificamerican.com/article/genetic-engineering-could-make-a-covid-19-vaccine-in-months-rather-than-years1 (2020).
[2]Biologicals: DNA Vaccines.
https://www.who.int/biologicals/areas/vaccines/dna/en/
[3]Khan, Kishwar Hayat. \”DNA vaccines: roles against diseases.\” Germs 3, no. 1 (2013): 26.
[4]“National Institutes of Health. \”Novel coronavirus structure reveals targets for vaccines and treatments (2020).\”
[5] Baeshen, Nabih A., Mohammed N. Baeshen, Abdullah Sheikh, Roop S. Bora, Mohamed Morsi M. Ahmed, Hassan AI Ramadan, Kulvinder Singh Saini, and Elrashdy M. Redwan. \”Cell factories for insulin production.\” Microbial cell factories 13, no. 1 (2014): 141.
About the Author
Jyotsna Nair is a 16 year old currently living in India. She is a rising senior, whose favourite subjects include math and biology. She hopes to do research in molecular biology in college, and enjoys reading and writing as well.
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