COVID-19 disease, caused by SARS-CoV-2 virus, has been steadily increasing in the past few months around the world with no end in sight. Till date, there has been no vaccines approved for curing for this debilitating disease that has infected around 2 million people globally and causing death in about 120,000 of them (1), a figure of 6%. This 6% mortality rate is the worldwide average, with European Union having a mortality rate of around 10% while the rest of the world having a mortality rate of around 3%. There has also been a recovery of around 450,000 people, a figure of around 23%.
Pharma and biotechnology companies along with universities and research institutes around the world are working with great fervour to develop a vaccine against COVID-19 that could become the saviour of people and prevent them for getting the disease. This article will focus on the concept of vaccine development for viruses, the types (category) of vaccines being developed for COVID-19 by numerous companies, institutes and consortiums around the world who are engaged in its research and development and its present status with emphasis on vaccine candidates that have already entered clinical trials.(1).
Vaccine development for viruses involves making a biological preparation of viral molecules consisting of live attenuated virus, inactivated virus, empty viral particles or viral peptides and protein(s) alone or in combination, which once injected into a healthy individual, triggers its immune system to produce antibodies against the viral molecules, thereby protecting the individual when actual infection happens. These viral molecules and proteins that act as antigens, can either be generated outside (in the laboratory) or produced (expressed) inside the individual (host) to generate the immune response. The technological advancements in the field of biotechnology in the past decade or so has played an important role in vaccine development as well, resulting in novel approaches for the production of viral antigens within or outside the host individual, that have contributed to the vaccine safety, stability and ease of large-scale manufacturing.
The types of vaccines under development for COVID-19 fall into three broad different categories based on the nature of technology platforms to generate viral antigens (2). The first category comprises of using the live attenuated vaccine (that involves weakening the virulence of SARS-CoV-2 virus) or inactivated virus (in which the inactivation is performed using chemical means) and injecting it in the host to develop an immune response. This category represent the way in which vaccines were made conventionally. The second category in vogue focuses on the production (expression) of viral proteins inside the host (humans) by use of nucleic acids (plasmid DNA and mRNA) and viral vectors (replicating and non-replicating) containing viral genes. These nucleic acids and viral vectors use cellular machinery for the expression of viral proteins within the host upon injection, thereby triggering an immune response. The third category involves development of empty (without genome) viral like particles (VLPs) expressing viral proteins on their surface, use of synthetic peptides (selected parts of viral proteins) and recombinant production of viral proteins as antigens in various expression systems at a large scale outside the human host, and then using them as vaccine candidates alone, or in combination.
As of April 10th 2020, a total of 69 companies, research institutes, universities and/or a consortium of the above (3, 4) are actively engaged at an unparalleled speed in a race against time for the development of COVID-19 vaccine. These companies can be divided into either of the three categories mentioned above based on the technology they are using for COVID-19 vaccine development. Seven of these companies are exploiting the way vaccines are manufactured by the first category and the remaining 62 companies are almost equally divided (30 in the second category which uses plasmid DNA, RNA and replicating and non-replicating viral vectors while 32 in the third category which uses VLPs, peptides and recombinant viral proteins) in terms of the technologies used for vaccine manufacturing for COVID-19. Most of these companies are in exploratory or pre-clinical stages of research and development. However, six of these companies have advanced their candidate vaccines into clinical trials which are listed in Table I (information sourced from references 2-6). All these vaccines fall into the second category.
Vaccine development for COVID-19 based on the technology platforms used belong 10% to first category and 43.5% to category two and 46.5% to category three respectively (Figure 1). Based on the geographic location, North America (USA and Canada) leads COVID-19 vaccine development with highest percentage of companies (40.5%) followed by Europe (27.5%), Asia and Australia (19%) and China (13%). Refer to Figure 2.
Figure 1. Categories of COVID-19 vaccine development
|S.No.||Vaccine Name And characteristics||Status||Clinical trial details||Companies/Institutes In collaboration||Country|
|1.||mRNA-1273: LNP (lipid nano particle)-encapsulated mRNA expressing S protein||Phase I (NCT04283461)||45 subjects, 18-55 years of age, will get administered an intramuscular injection of mRNA-1273 on Day 1 and 29 in the deltoid muscle and will be followed through 12 months post second vaccination (Day 364)||Moderna therapeutics and NIAID (National Institute of Allergy and Infectious Diseases)||USA|
|2.||Ad5-nCoV: Adenovirus type 5 vector expressing S protein||Phase I (NCT04313127)||108 subjects, 18-60, will receive an intramuscular injection of Ad5-nCoV (low, medium and high doses) in the deltoid muscle||CanSino Biologics||China|
|3.||ChAdOx1 nCoV-19: Chimpanzee adenovirus vector||Phase I||510 subjects, 18-60, will receive an intramuscular injection of ChAdOx1 nCoV-19, participate for 6 months with the option to come for an additional follow up visit at day 364||University of Oxford||UK|
|4.||INO-4800: Plasmid DNA encoding S protein||Phase I (NCT04336410)||40 subjects, 18-50, will receive two doses of INO-4800, each of 1.0 mg, four weeks apart administered through the skin||Inovio Pharmaceuticals Inc||USA|
|5.||LV-SMENP-DC: Dendritic cells modified with lentiviral vector expressing synthetic genes based on domains of selected viral proteins; administered with antigen-specific cytotoxic T lymphocytes||Phase I (NCT04276896)||100 subjects will receive approx. 5 million dendritic cells or 100 million Cytotoxic T Lymphocytes as a single infusion via sub-cutaneous route||Shenzhen Geno-Immune Medical Institute||China|
|6.||Pathogen-specific aAPC: artificial Antigen Presenting Cells expressing synthetic genes based on domains of selected viral proteins||Phase I (NCT04299724)||100 subjects will receive approx. 5 million aAPC cells each time via sub-cutaneous route at 0, 14 and 28 days.||Shenzhen Geno-Immune Medical Institute||China|
Figure 2. Geographic distribution of companies engaged in COVID-19 vaccine research and development.
The majority use of categories 2 and 3 in vaccine development for COVID-19 suggests the exploitation of modern state of the art technologies that have led to the ease of manufacturing and might contribute to the safety, stability and effectiveness of vaccine preparations. It is sincerely hoped that the current vaccines in clinical trials and the ones that follow would result in an effective vaccine candidate that can be fast tracked for approval by the regulatory authorities for vaccinating the human population, thereby preventing them from contracting the COVID-19 disease, and overcoming the misery that has been caused by this debilitating disease.
1. Worldometer 2020. COVID-19 CORONAVIRUS PANDEMIC. Last updated: April 14, 2020, 08:02 GMT. Available online at https://www.worldometers.info/coronavirus/ Accessed on 13 April 2020.
2. Thanh Le T., Andreadakis, Z., et al 2020. The COVID-19 vaccine development landscape. Published 09 April 2020. Nature Reviews Drug Discovery DOI: http://doi.org/10.1038/d41573-020-00073-5
3. Milken Institute, 2020. COVID-19 Treatment and Vaccine Tracker. Available online at https://milkeninstitute.org/sites/default/files/2020-03/Covid19%20Tracker_WEB.pdf Accessed on 13 April 2020.
4. WHO, 2020. DRAFT landscape of COVID-19 candidate vaccines â€“ 20 March 2020. Available online at https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf?ua=1 Accessed on 13 April 2020.
5. Regulatory Focus, 2020. COVID-19 Vaccine Tracker. Available online at https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker Accessed on 13 April 2020.
6. USNLM 2020. COVID-19 Clinical Trails Available online at https://www.clinicaltrials.gov/ct2/results?cond=COVID-19 Accessed on 13 April 2020.
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