The Quest for the COVID-19 Vaccine

Updated: Dec 31, 2020

By Sreenidhi Sankararaman



Virus; Credit: U.S. Food and Drug Administration

BACKGROUND OF COVID-19

The origins of COVID-19, or the coronavirus disease, is currently unknown. Although many theories exist about the origins of COVID-19 in Asia, there is no concrete evidence to support these theories. One theory is that COVID-19 arose in the Wuhan Institute of Virology in China, an institute that analyzes viruses associated with bats and the genomes of these viruses. This theory arose due to the fact that the Wuhan Institute of Virology is located near the live animal Wuhan market in which early cases of COVID-19 were detected in December. Critics, have speculated that the COVID-19 disease could have been released into the market due to low biosecurity measures in the institute. However, further microanalysis of the genome of the COVID-19 virus indicates that this theory is not plausible as the virus does not have a structure that seems to have been engineered or built off of a previous, or existing, virus structure. Although the origins of COVID-19 are unknown, the virus shows a striking similarity to zoonotic viruses from bats. After researchers analyzed the genome of the virus in the Wuhan Institute of Virology, they found that the genome was very similar to coronaviruses from horseshoe bats. In the past, such zoonotic diseases have been looked over as many people believed that these diseases from animals could not harm humans. However, after zoonotic diseases from bats, such as SARS and MERS which impacted millions of people across the world, the world has grown to fear such zoonotic diseases. In the transmission of coronaviruses, such as COVID-19, an intermediate animal is necessary if the disease is to pose any harm to a human. Originally, snakes were thought to be the intermediate between bats and humans in the transmission of COVID-19. However, this possibility was ruled out after researchers found that a strain of coronavirus in pangolins, a type of anteater, had a 91% similarity to COVID-19, indicating that pangolins were indeed the intermediate animal for this zoonotic virus. To address over 5 million cases of COVID-19 worldwide and over 400,000 deaths, researchers are analyzing how pangolins are able to remain unaffected as carriers of COVID-19 to engineer a vaccine for COVID-19.

VACCINE INTRODUCTION

In engineering a COVID-19 vaccine, many considerations need to be taken into account. To begin with, the safety of the vaccine needs to be tested. Although animals have been used to test the safety of potential COVID-19 vaccines, the vaccines have never succeeded in preventing complete infection. The tested vaccines have only been partially successful in improving survival. Even along the lines of improving the survival of the patient, the vaccine also needs to be tested to ensure that it can prevent reinfection by lingering remnants or dormant remnants of the original COVID-19 virus. The next consideration when making a vaccine is considering the mechanism of vaccination. The purpose of a vaccine is to activate a patient’s immune system to make target antibodies to fight against the virus at the moment of infection and memory antibodies to be able to fight against the virus if a recurrence of the virus occurs. Types of potential vaccines include live vaccines, which are weaker forms of the virus. Because this form is weak, the immune system is given time to recognize the antigens of the virus but is not directly harmed by the introduction of the virus. This recognition of the antigens can be later used to fight the stronger, original virus. Another type of vaccine is inactivated vaccines, which are dead viruses which the patient’s immune system can use to learn about the antigens and characteristics of the original virus. Genetically engineered vaccines utilize RNA and DNA to make S proteins that are used to activate the immune system of the patient. All of these considerations are required to make a successful vaccine for COVID-19.

TYPES OF VACCINES

Although there is no concrete COVID-19 vaccine being distributed currently, many candidates for the COVID-19 vaccine are being considered. The first example is the mRNA-1273 vaccine introduced by Moderna, a health company. This vaccine consists of a lipid-nanoparticle vector that contains a S-protein, or viral spike protein, whose purpose is to boost the patient’s immune system. Moderna conducted a study to test the effectiveness of the mRNA-1273 vaccine by giving 8 candidates the lowest dose (25 mg) and the middle dose (100 mg). The results showed that neutralizing antibodies for the coronavirus were generated to the extent of the antibodies generated when a person recovered from COVID-19. However, an issue arises with the limited sample size and also the fact that older people would need a more tailored vaccine as their immune systems do not respond as well to vaccines. In addition, another issue that arises with this vaccine is that patients often developed redness when given more than 100 mg and for certain patients, the levels of antibodies significantly exceeded those of a healthy person. Another example of a vaccine is Ad5-nCoV, which is an adenovirus vector vaccine (gene carriers holding active viral genes) that also contains the S protein that was developed in China. Adenovirus vectors indicate that the vector or virus were first discovered in adenoid tissue. This vaccine uses the common cold virus to introduce viruses spiked to cells to trigger the immune system of a patient. The first human trial of Ad5-nCoV on May 22, 2020 shows that 1 dose of Ad5-nCoV in a human patient led to the development of killer cells for the virus and antibodies specific to the COVID-19 within 14 days. One issue with the vaccine is that 75% of the candidates given a high dosage reported negative side effects within 7 days. However, this vaccine shows great promise as a potential vaccine candidate. Another example of a potential vaccine is INO-4800. Developed by Inovio, this vaccine delivers DNA plasmids to the cells that work to generate proteins through transcription and translation that can activate the immune system and produce T-cells, or killer cells of the virus, to fight off coronavirus. Phase 1 testing of INO-4800 in humans has only recently begun and results for this vaccine’s success are expected in June 2020. Another example is LV-SMENP-DC. This vaccine addresses dendritic cells, which are cells that present antigens and act as an interface between immune systems. It uses lentiviruses, or a type of retroviruses, to modify dendritic cells to present COVID-19 antigens to activate the immune system. This leads to the production of cytotoxic T-lymphocytes which target and kill the COVID-19 virus. However, an issue with this type of vaccine is that the safety and efficiency of this vaccine have yet to be tested. Hence, this prevents its implementation on human patients for COVID-19. Finally, another potential candidate for vaccine is pathogen-specific aAPC. This vaccine examines protein domains of the virus and makes mini lentiviral, or retroviral, genes to express COVID-19 antigens to activate the immune system. The safety of this vaccine and the safety of dosages at different times (0, 14, 28 days) are currently being tested. In terms of a feasible candidate of a COVID-19 vaccine, a vaccine has recently been developed in Oxford. Also known as ChAdOxl nCoV-19, this vaccine is one of the leading vaccines in the world against COVID-19. This vaccine targets the virus’s spike protein, or infecting mechanism, which ensures that the disease will not have the ability to increase its infectivity. However, this vaccine only has a 50% success rate among its patients. The above information of potential vaccines and relatively feasible vaccines shows that, although the world does have its work cut out for it regarding vaccines for COVID-19, significant progress has been made.

CONCLUSION

COVID-19, originally only seen in Asia, has grown to impact the entire world. COVID-19 has reached every continent, except for Antarctica, and has resulted in millions of cases and thousands of deaths worldwide. Although researchers are piecing together the story of COVID-19, from its origins, to its intermediates and methods of transmission, more work is still required to engineer a successful and feasible vaccine. Potential candidates include retrovirus technology, viral vector machines, adenovirus vectors, spike protein removal technology, and various other technologies. However, the success of these vaccines is yet to increase above a 50% success rate. As a global society, it is our responsibility to respond to the challenges posed by COVID-19 by ensuring sanitization, reporting cases to WHO, gathering information about COVID-19 mitigation, and helping in the dissemination of this information. Through the work and efforts of researchers and scientists, the world will hopefully be able to use existing knowledge and discover new ideas to prevail against COVID-19.


Resources:

1. https://www.worldometers.info/coronavirus/countries-where-coronavirus-has-spread/

2. https://journals.sagepub.com/doi/full/10.1177/2516602620938542

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4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192075/

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147684/

6. https://courses.lumenlearning.com/boundless-biology/chapter/proteins/

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11. https://www.fda.gov/food/food-safety-during-emergencies/food-safety-and-coronavirus-disease-2019-covid-19

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