Vaccines under clinical trials to prevent Covid-19 - An article by Aliva Basu

The author is B. Pharm student from NMIMS-SPPSPTM

Introduction

Covid-19 or also known as Coronavirus disease is an infectious disease which has rapidly emerged to become a global pandemic. The main reasons why it is so dangerous is because it takes about 2 weeks for the symptoms (coughing, fever and in severe cases, respiratory distress) to develop and thus be identified. In that period, the infected person can transmit this disease to countless other people they come in contact with through cough or sneeze droplets.^[1] Another reason for it’s danger lies in the survival mechanism of the virus causing the disease. Covid-19 is caused by the virus SARS-CoV-2. This virus can remain stable and alive for several days on surfaces and in aerosols.^[2] The exact mechanism for this disease is yet not known and is still under research but there are several theories proposed. The pandemic is a huge risk to global health with more than 1,500,000 cases reported worldwide till date and more cases emerging at a quick pace has spurred various countries to develop a vaccine or treatment.

At present, there is no affirmed vaccine for Covid-19. The family of the virus SARS-CoV-2, Coronaviruses, have been known to cause other deadly diseases like MERS and SARS which are also deadly but better contained than Covid-19. There are various vaccines on trial for these diseases which are also being pursued for treating Covid-19. The Coalition for Epidemic Preparedness Innovations, or CEPI, is an association assisting in quickly developing a vaccine. Around 35 organizations and scholarly foundations are looking for a Covid-19 immunization; around 4 of them are on stage 1 of their clinical trials, and more than 40 in preclinical improvement.^[3]

Vaccines in Clinical Trials

Kaiser Permanente Washington Health Research Institute (KPWHRI) has started an investigation on a special type of messenger RNA vaccine termed as mRNA-1273 in collaboration with Moderna inc. in Seattle,Washington. The study is being subsidized by The National Institute of Allergy and Infectious Diseases (NIAID) which is under National Institute of Health (NIH). The study is said to be conducted over a period of one and a half months with 45 healthy volunteers between the age of 18 to 55. The examination is assessing various portions of the trial immunization for security and its capacity to incite an insusceptible reaction in participants. This is the first of various strides in the trial procedure for assessing the potential advantage of the immunization.^[4]

On 6 April 2020, Inovio Pharmaceuticals in collaboration with a Chinese company started clinical trials for a DNA vaccine termed INO-4800. They are backed by Gates Foundation and CEPI.The study is being conducted in America with a total of 40 volunteers.^[5] Jenner Institute of the University of Oxford reported that along with Advent, they had built up an vaccine applicant which is dependent on an adenovirus vector called ChAdOx1 nCoV-19.^[6][7] Another corporation joining the above mentioned companies is CanSino Biologics Inc. who are developing their own recombinant adenovirus called Ad5-nCoV. Both of the studies have a clinical trial with human volunteers - 510 and 108 in number respectively.^[8][9]

Sr.No	Company	Vaccine/Vaccine type	Stage of development
1.	Moderna\KPWHRI	mRNA 1273	Phase I Clinical Trial
2.	Inovio	INO-4800	Phase I Clinical Trial
3.	CanSino Biologics Inc.	Ad5-nCoV	Phase I Clinical Trial
4.	University of Oxford	ChAdOx1 nCoV-19	Phase I Clinical Trial

Table 1 shows the vaccines currently undergoing their clinical trials

Vaccines in Preclinical Research

There are many organisations who have taken an interest in developing a vaccine for Covid-19.  Evvivax and Zydus Cadila are working on developing vaccines focusing on DNA.  Janssen (Ad26 ), Altimmune (adenovirus based NasoVAX expressing SARS2-CoV spike protein) and Greffex (Ad5 S) are focusing on developing viral vectors. University of Saskatchewan (Adjuvanted microsphere peptide), Vaxil Bio (Peptide), AJ Vaccines  (S Protein), Novavax       (VLP recombinant protein nanoparticle vaccine + Matrix M) are working on using subunits of protein in vaccination. Big Pharma companies like GlaxoSmithKline, Sanofi and Johnson & Johnson also announced that they are both working on developing a vaccine. Some other vaccines are listed below in table 2.^[10]

Company	Vaccine/ Vaccine type	Platform		Company	Vaccine/ Vaccine type	Platform
University of Queensland in Australia	Viral protein cell culture	Protein Subunit		Codagenix/ Serum Institute of India	Deoptimized live attenuated vaccines	Live Attenuated Virus
CureVac	mRNA vaccine	RNA		GeoVax/ BravoVax	MVA encoded VLP	Non Replicating Viral Vector
Karolinska Institute / Cobra Biologics	DNA with electroporation	DNA		Heat Biologics/ University of Miami	gp-96 backbone	Protein Subunit
Zydus Cadila	DNA plasmid vaccine	DNA		DZIF–German Center for Infection Research	MVA-S encoded	Non Replicating viral vector
Tonix Pharma/ Southern Research	Horsepox vector expressing  S protein	Replicating Viral Vector		NIID, Japan	S protein +Adjuvant	Protein Subunit

Table 2 shows some vaccines undergoing preclinical trials

Aside from immunizations, almost 70 medications and exploratory mixed potions are being inspected for treatment. Medications include an antiviral compound called Remdesivir; antimalarials Chloroquine and Hydroxychloroquine; a blend of two HIV drugs, Lopinavir and Ritonavir; and Interferon-beta. There are other types of homologous formulations of Monoclonal Antibodies and Plasma derivatives which are also being surveyed. Another potential interest or area is Stem cells.^[11]

In spite of the rapid exploration, there are a few parts of the developmental procedure that cannot be accelerated, as every clinical trial requires boundless testing for symptoms and dosing. And still, after all that, there are strategic obstacles to scaling creation and circulating vaccines to the influenced nations. Specialists are anticipating it will take a year and a half for an immunization to be generally accessible.

References

1. https://qz.com/1822554/how-the-coronavirus-tricks-cells-into-a-full-body-invasion.

 (Accessed on 9/4/2020)

2. N van Doremalen, et al. Aerosol and surface stability of HCoV-19 (SARS-CoV-2)                               compared to SARS-CoV-1. The New England Journal of Medicine. (2020).
3. https://www.digitaltrends.com/health-fitness/coronavirus-covid-19-vaccines-treatments-list.  (Accessed on 9/4/2020)
4. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins. (Accessed on 9/4/2020)
5. http://ir.inovio.com/news-and-media/news/press-release-details/2020/INOVIO-Initiates-Phase-1-Clinical-Trial-Of-Its-COVID-19-Vaccine-and-Plans-First-Dose-Today/default.aspx.  (Accessed on 10/4/2020)
6. https://www.jenner.ac.uk/about/news/novel-coronavirus-vaccine-manufacturing-contract-signed. (Accessed on 10/4/2020)
7. https://www.telegraph.co.uk/global-health/science-and-disease/vaccine-hunters-racing-save-world-coronavirus-pandemic. (Accessed on 10/4/2020)
8. https://www.theguardian.com/world/2020/mar/27/uk-scientists-enrol-volunteers-for-coronavirus-vaccine-trial. (Accessed on 10/4/2020)
9. https://www.bioworld.com/articles/433791-china-approves-first-homegrown-covid-19-vaccine-to-enter-clinical-trials. (Accessed on 11/4/2020)
10. https://www.who.int/blueprint/priority-diseases/key-action/Novel-Coronavirus_Landscape_nCoV-4april2020.pdf?ua=. (Accessed on 11/4/2020)
11. https://www.healthline.com/health-news/heres-exactly-where-were-at-with-vaccines-and-treatments-for-covid-19. (Accessed on 12/4/2020)