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REVIEW ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 2  |  Page : 105-109

Vaccine in response to COVID-19: Recent developments, challenges, and a way out


Department of Genetics, Indian Academy Degree College; Founder and CEO, GenLab BioSolutions Private Limited, Bengaluru, Karnataka, India

Date of Submission03-Sep-2020
Date of Acceptance14-Mar-2021
Date of Web Publication16-Jun-2021

Correspondence Address:
Mr. Sameer Quazi
Department of Genetics, Indian Academy Degree College, Bengaluru, Karnataka; GenLab BioSolutions Private Limited, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_166_20

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  Abstract 


Severe acute respiratory syndrome coronavirus 2 proved to be disastrous as it affected a large population in the period of a few months. As the virus took hold in the world, health experts paced efforts to solve the unknown nature of this threat. Besides finding short-term and sudden relief, scientists directed their efforts to provide a long-term solution for an ensuing pandemic that influenced all areas of life in unprecedented ways. The subject matter of this research involves exploring the relevant literature regarding passive immunity in fight against the virus. It is expected that different vaccine platforms such as traditional recombinant protein, macromolecule DNA and mRNA, and nonreplicating and replicating viral vectors could be helpful if utilized properly. This article is going to discuss all these platforms and recent developments regarding the formulation of the vaccine. It is going to highlight the need for the production and distribution of the medicines along with challenges that are present in this task. The facts involving social, political, and economic aftermath would also be discussed in the current research. There is no doubt that biotechnology is going to provide a sound foundation to fight with upcoming health-related challenges. Along with the exploration of this fact, the article is going to prove a case for effective collaboration among all stakeholders such as government, academia, health sector, and civil society. The mechanism of collaboration would produce safety and efficacy data with the help of many volunteers, to speed up the distribution of multiple vaccine platforms to fight against COVID-19 and to strive for a better future.

Keywords: Bharat biotech, covaxin, economy, Middle East respiratory syndrome, severe acute respiratory syndrome, vaccine development


How to cite this article:
Quazi S. Vaccine in response to COVID-19: Recent developments, challenges, and a way out. Biomed Biotechnol Res J 2021;5:105-9

How to cite this URL:
Quazi S. Vaccine in response to COVID-19: Recent developments, challenges, and a way out. Biomed Biotechnol Res J [serial online] 2021 [cited 2021 Aug 2];5:105-9. Available from: https://www.bmbtrj.org/text.asp?2021/5/2/105/318443




  Introduction Top


The obsession of power led human beings to neglect social factors while making progress in the fields of defense, economy, and technology. Threatening each other with the military might, no one had the slightest idea that something so trivial could bring the world to a halt. Originating in unexpected circumstances, the novel coronavirus threatened the whole humanity. The structure of COVID-19 was unknown so nothing could be prescribed for the treatment and trials started to find a solution for this problem. It burdened the healthcare system to its maximum capacity and put a strain on the global economy in unimaginable proportions. However, the most significant loss was incurred in the human lives as >400,000 people are lost in just 6 months of origination of this virus, and the number is increasing day by day. The globalization made the task more difficult as people were unaware of its severity and made continuous contact with each other daily.


  Conducting High-Quality Research on COVID-19 Vaccines Top


At this moment, all eyes are turned to the healthcare industry and professionals to get the world out of this calamity. However, the task is not as easy as it seems. In present circumstances, the difficulty increases two-fold as clinicians are not only responsible for providing care to patients but also need to take necessary precautions to save their lives from a deadly virus. Despite this, the contributions of healthcare providers remain praiseworthy throughout the world. It is imperative to develop a vaccine that provides immunity to the population of the world because there is no natural immunity to this virus due to its unique nature. There are many academic and pharmaceutical companies across the world, including India that are trying to provide a swift solution for the strain severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). The road is not smooth, and various challenges are being encountered in achieving this feat.

The nature of this disease implies that any solution that is provided should offer long-term protection and vaccines fit the description well. Vaccines are predominantly biological agents that fight against a specific antigen derived from a pathogen, causing infectious diseases.[3] They provide immunity against a particular disease, helping in both prevention and medication. There are two main types of vaccines that fight against lethal infections. The first ones are those that use the whole pathogen in their manufacturing, including live attenuated and inactivated vaccines. Both types contain wild viruses and bacteria; however, in live attenuated, the pathogen is weakened, and in an inactivated vaccine, the pathogen is inactivated before inculcation. The other classification uses only a fragment of the pathogen in their manufacturing and is known as subunit vaccines. It includes toxoid vaccine formed with inactivated toxins, conjugate-polysaccharide vaccine derived from the outer layer of encapsulated bacteria and carrier proteins, and a recombinant vaccine in which a segment of genes containing disease-causing protein is inserted into a gene of another cell where it replicates and provides protection against the infection.[17]


  Vaccine Action Against Infections Top


With the introduction of the first vaccine in 1796, Edward Jenner paved the way for the eradication of several infectious diseases. The first vaccine was developed against smallpox using cowpox. After that, considerable advancements have been made in the field of vaccination and immunization.[3] Vaccine develops immunity by imitating infection. When an infection is introduced in the body, the body immune system begins manufacturing T-lymphocytes as well as B-lymphocytes. These cells possess the ability to fight against that particular viruses. Even after the imitated infection is removed, the body becomes able to fight against this infection in the future. The introduction of imitated infection seldom causes illness. Minor symptoms such as fever are a regular occurrence, as the body is preparing to fight against germs.[2] However, if the person is infected immediately before or after the vaccine may develop symptoms of the disease as the vaccine takes a couple of weeks to build immunity in the body.

Vaccines are characterized by a proactive approach that helps to operate swiftly and efficiently. Different methods have been applied for vaccine development, such as traditional recombinant protein, macromolecule DNA and mRNA, and nonreplicating and replicating viral vectors.[16] However, every platform comes with certain advantages and drawbacks. Usually, a multipronged approach is used to fight against one disease. A vaccine must be able to fulfill specific attributes such as safety, reactogenicity, the versatility of manufacture, longevity of immunity, production scale and price, vaccine stability, and cold chain requirements.[4]


  Developments in Immunization Against COVID-19 Top


Just as in the cases of many other deadly infections, efforts to provide a solution for novel coronavirus disease started as soon as the world realizes the lethal nature of this virus. Although on a trial basis, the efforts made by the health sectors of many countries provided hope for humanity. In this regard, many pharmaceutical companies remain prominent. Replication-defective adenovirus 26 (rAd26), a product of Janssen Pharmaceuticals proved to be secure and immunogenic in the prevention of Ebola Virus.[5] Similarly, recombinant chimpanzee Ad vector (ChAdOx1) entered clinical trials by the University of Oxford along with AstraZeneca (2020). It was also founded safe and immunogenic in prior clinical trials.[12] Tests on humans are also underway in Germany and the USA as the Pfizer and BioNTech pharmaceuticals claimed in May. On an emergency basis, a drug is also introduced and approved in severe cases of coronavirus infection. Gilead Sciences named this broad-spectrum antiviral medication Remdesivir specific to the treatment for COVID-19 infections.[13],[14] An antibody treatment drug that is produced by Regeneron and some other companies is also available.

Based on prior studies, mRNA-1273, manufactured by Moderna, also showed significant feasibility in the case of coronavirus.[16] The cases of SARS and the other virus of a similar category, the Middle East respiratory syndrome, showed significant improvement. Doses of either 25 μg or 100 μg successfully neutralized the antibody titers in eight participants.[9] The second phase of the trial using mRNA-1273 was started on May 29, and the third phase using 30,000 volunteers initiated in July, funded by operation warp speed. It differs from other pharmaceuticals, Johnsons, in a number of respondents in research trials. Moderna chose a large number of people while Johnsons selected fewer candidates in Boston.[18] The research by Johnsons utilized the collaboration with Biomedical Advanced Research and Development Authority BARDA. They chose a prime candidate for vaccine trial with two backup candidates. Sanofi is another company that is funded by BARDA and plans to initiate the Phase ½ trial in September. It is using the platform of recombinant DNA along with Translate Bio utilizing the previous work on SARS vaccine to provide both instant and long-term relief.
Table 1: Examples of vaccines

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Recently, the health sector of India is also engaged in efforts to develop the vaccine for deadly COVID-19 virus. The Serum Institute of India is already collaborating with the Jenner Institute of Oxford University that is involved in providing vaccine in less possible time. However, the most striking work is underway in the leading vaccine development company of India that is Bharat Biotech. It has already contributed so many vaccines for infections such as rotavirus, hepatitis, Japanese encephalitis, and Zika virus. To develop a vaccine for novel coronavirus, the Bharat Biotech is working in collaboration with the Indian Council of Medical Research and the National Institute of Virology. They are working on designing inactivated vaccine which they named as Covaxin and is underway in high containment facility Bio Safety Level 3 BSL-3 under Bharat Biotech. Approved by the Drug Controller General of India, the vaccine is expected to be launched by the 15th of August for public use after completing the mandatory clinical checks. Along with this, Bharat Biotech is also working closely with the vaccine candidate of the University of Wisconsin and the other with Thomas Jefferson University.[10] The varied perspectives are underway around the world and provide an opportunity for modular production essential for widespread population use.


  Challenges in Vaccine Development in Response to Severe Acute Respiratory Syndrome Coronavirus 2 Top


Despite the developments in the field of immunization and vaccination, particular challenges always arise due to the nature of the virus under test. These challenges make it more challenging to produce a vaccine quickly and without any flaws. In the case of COVID-19, there are so many challenges besides the technical problems that always slow down the process. It includes the deadly nature of coronavirus that demands an efficient precautionary procedure to follow that ensures the safety of life of first respondents. Besides dealing with the risk of contracting disease, its unique and novel nature is natural to create misinterpretations and miscalculations. The other challenges are as follows:

Ensuring vaccine safety

The concept of vaccine safety remains vital in the field of immunization. In the case of coronavirus, the life of a person is involved who just contracted the disease. Previous studies showed that many vaccines for SARS had been tested on animals. Although the vaccines helped in the survival of animal yet did not help in preventing the infection. In the case of coronavirus, many studies proved that patients who are cured again developed the symptoms in specific situations. Furthermore, the novel coronavirus is known to damage the different organs and the patient cannot risk more such complications. Therefore, the vaccine needs to be thoroughly tested and tried to make it secure for future use on human beings.

Providing long-term protection

Vaccines are different in their actions as they provide long-term protection as opposed to the drugs that are usually effective for a short time. The coronavirus is unique as cases of re-infections emerged throughout the world. Although circumstances are fewer, they threatened the effectiveness of vaccines that are under trials.[15] Vaccines should be developed after clearly understanding the nature of COVID-19 virus strain. Only after careful trials, the vaccine could be developed for long-term protection.

Protecting older people

When novel coronavirus began affecting the world population, the older people got more infection, and their mortality rates also increased. Due to their weak immune systems, they are at higher risk for contracting the coronavirus disease.[15] As they do not respond to vaccines as the young population do, it became a challenge for health care companies to introduce inactivated vaccines that prove too effective in the high-risk population. Researchers should also deliberate on providing different vaccines for varied age groups.

Highly mutagenic

Experts have also made an alarming discovery regarding this virus that it changes strain frequently. There is a possibility that it may alter its structure from person-–to-person. This quality makes it more lethal as one type of vaccine may not be enough if different forms of the mutant virus are present across the world.[6]

Besides these challenges, the world is also fighting on other fronts after the attack of the novel coronavirus. The responsibility lies with the communist party of china that deliberately let this virus spread across the world and changed its status from endemic to pandemic. They could have contained the virus in various ways, such as imposing travel restrictions on their citizens and sharing vital information with the world. Although bashing would serve no useful purpose yet the accountability should be ensured as to avoid any other such mishap that could threaten the whole world.


  Repercussions Top


The aftermath of this virus could be drastically different than the one expected a year ago. The era of globalization would suffer a significant setback as the countries would priorities the lives of their citizens and would mostly rely on the local supply chain. The self-dependence, though appreciative in many ways, could lead to more intolerance and violence around the world. Although the virus set many examples of altruism, yet the power struggle has not seen to be diminished soon. It could be expected that an arms race would ensue to get in the race of power struggle. It would not only cause human casualties but also bring the human development index to a new low. Poverty, hunger, and unemployment would pace up the crime both on the local and global level. According to the International Labor Organization (2020), 25 million jobs would be lost due to the disease.[7] The sectors that are at increased risk include tourism, hospitality, aviation sports league, and the international education industry. They may face stunted growth for the next 2 years. In the absence of government support, companies may file for bankruptcy, as seen in the aviation industry. The technology could also be used to serve the interests of specific groups, further initiating the mental health concerns in the world.

In the economic front, the volatility is beginning to show in the financial markets. According to the Asian Development Bank ABD (2020), the global economy would suffer a loss of 5.5–8.8$ trillion due to this pandemic.[1] It is almost equal to two-three times India's GDP. This shock has predominantly induced the capital and liquidity risks that not only threatened the investments and credit intermediation but also damaged the households and various companies. The economy and financial systems could be at risk with such massive damage that looks like a speed bump in economic growth but could have long-term effects.


  Biotechnology: A Way Out Top


Humanity has faced daunting situations in the past but remained victorious. Coronavirus has made us realize the importance of preparation for an epidemic, although it is going to be expensive but would cause a lesser dent on our economies in such a crisis. The world must prepare because it will not be the last pandemic to hamper millions of lives, but there would be many such incidences in the future. Biotechnology has excellent potentials in combating such attacks and providing a one-point solution. Two fundamental aspects biotechnology can provide is the speedy research and large-scale manufacturing of vaccine. Over the past decade, technology such as DNA sequencing, DNA synthesis, genetic engineering, immunoinformatic has become more advance and economically viable, which can play a crucial role in developing a vaccine against coronavirus. The best example is the biotech start-up “Moderna Therapeutics,” which has successfully developed an mRNA vaccine against SARS-CoV-2 and is under the first clinical trial.[18],[19] The mRNA vaccines do not rely on any kind of laboratory culturing or bioreactors and can be synthesized using chemical methods. The mRNA is easy to pack into a delivery vehicle having a chemical structure called lipid nanoparticles, which boosts the uptake of the vaccines in our body.[16] Thus, it is potentially faster, safer, and cheaper than any other type of vaccine, certainly designed and manufactured more quickly during new pandemics.

There are many ways a vaccine works to tackle an infection. One of which involves neutralizing antibody. However, the manufacturing and course of action are reliant on the type of infection. Sometimes, a strain-specific vaccine is effective; other times, no vaccine may work. COVID-19 comes under the category of the highly mutating virus, and a technique known as immune-focusing can be utilized to target different strains of the same virus. In normal circumstances, the common epitope is influenced by antibody, and the only alteration of amino acid is done to transform the vaccine over the years. In case of immune focusing, those domains are focused for which infected host rarely produce antibody, dies and amino acids remain conserved.[8] A vaccine targeting the specific domain could protect for many years. However, these strategies have diverse drawbacks too as they are not easily generalizable. Furthermore, these immune-focusing techniques have low resolution and difficulty to maintain the 3D structure of the epitope, which is challenging. A comprehensive understanding of the specific epitope recognized by the antibody is valuable not only for antibody engineering but also for vaccine design.[2]

At present, there is no immunogen available that can influence COVID-19 neutralizing antibodies and the need to manufacture and dispense safe and effective vaccines is striking. It can immunize an exceptionally huge number of individuals protecting the universal coterie of the continued threat of medical issues and mortality from SARS-CoV-2.[20],[21] There is a global need to adopt more than one effective approach for vaccines development due to the diverse nature of the pandemic. Biotechnology and pharmacology have an enduring bond that can be utilized in the development of a vaccine using a variety of approaches.[11] As far as COVID-19 is concerned, a single force is not enough to fight the lethal disease. It is a need of time that a government along with academia, and industry play their part. Their strengths would add up which provide the data and safety checks to form a variety of vaccines against SARS-COV-19 by collaborating with volunteers across the world.


  Moving Towards Better Future Top


With all these challenges and negativity, the virus inevitably brought the positivity in various segments of life. It teaches us self-discipline by compulsion of social distancing. The health came to the forefront, and people adopted healthy habits such as yoga and meditation. Culinary skills provided a way for strengthening the bond with family. The social consciousness also increased as people learned the importance of remote work and identifying the challenges that come in its way. The environment also got some respite from human activities such as traffic is reduced, pollution is controlled; nature became purer and is thriving again. It made people realize that only a will is needed to change the course of action and to strive for a better future of the earth.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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