The Headway of Coronavirus Vaccine

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Parvedge Haider

The Coronavirus has caused an ongoing pandemic around the world. The scientific name of this virus is ‘Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)’[1]. The disease has been termed as Coronavirus Disease (COVID-19). As of 18 March 2020, more than 208,000 cases of COVID-19 have been reported in at least 170 countries and territories, with major outbreaks in China, Iran and the European Union. The virus is primarily spread between people similar to influenza, via respiratory droplets from coughing and sneezing. There are relentless efforts in many places for inventing the vaccine for countering this deadly virus. Currently about 20 vaccine development programs are in progress around the world. Very recently, a corona virus vaccine trial has been conducted in the U.S. to a human participant[2]. A healthy volunteer in Seattle, USA is the first person to receive a dose of an experimental coronavirus vaccine.

Photo-1: First person to receive a dose of an experimental coronavirus vaccine
Photo-2: 3D Structure of SARS-CoV-2
Photo-3: Electron Microscopic view of SARS-CoV-2 virus

During the discovery of this virus for the first time, scientists identified little spikes around the virus which appeared a look of the Corona of Sun.

Photo-4: Corona of Sun

The term ‘Corona’ has been originated from Latin word ‘Corona’ which means crown. So, the look of Corona is like a European style crown.

Photo-5: European style crown

The vaccine is funded and developed by NIAID (National Institute of Allergy and Infectious Diseases) scientists in collaboration with the biotech company Moderna Inc[3]. NIAID works under the aegis of National Institutes of Health (NIH) – the US medical research agency. Moderna’s study has made the most headway among efforts by the pharmaceutical industry to develop coronavirus vaccines as it is the first to be tested in human patients. Its vaccine uses synthetic messenger RNA (mRNA) to inoculate against the coronavirus. Such treatments help the body immunize against a virus and can potentially be developed and manufactured more quickly than traditional vaccines. Moderna joins BioNTech SE, a German drug developer working on mRNA-based treatments, which entered into a partnership with Shanghai Fosun Pharmaceutical[4] to develop and distribute a coronavirus vaccine in China.

The Trial of the vaccine has been conducted at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle. KPWHRI is a part of NIAID’s Infectious Diseases Clinical Research Consortium.

Photo-6: Kaiser Permanente Washington Health Research Institute

The vaccine is called mRNA-1273. The investigational vaccine directs the body’s cells to express a protein, hopefully that will elicit a robust immune response. The mRNA-1273 vaccine has shown promise in animal models, and this is the first trial to examine it in humans.

Photo-7: Spikes of Corona Virus

Messenger RNA, or mRNA, plays a fundamental role in human biology, transferring the instructions stored in DNA to make the proteins required in every living cell. The approach is to use mRNA medicines to instruct a patient’s own cells to produce proteins that could prevent, treat, or cure disease. If the vaccine works as designed, the immune system should generate antibodies that grab hold of a characteristic protein found on the surface of the novel coronavirus SARS-CoV-2.

This vaccine is not creating risk for the people; it does not contain any part of the actual coronavirus and cannot cause infection like the older generation vaccines. Instead, it includes a short segment of messenger RNA that is made in a lab.

As soon as Chinese scientists posted the genetic sequence of the new coronavirus on the internet, the other scientists started working on the vaccine since the January. However, one of the teams among the scientists already had been working on an investigational Middle East respiratory syndrome coronavirus (MERS-CoV) vaccine targeting the spike, which provided them with a head start. MERS-CoV first emerged in late 2012. Since its emergence, a total of 2279 patients from 27 countries have been infected across the globe according to a World Health Organization (WHO) report (Feb. 12th, 2019). Approximately 806 patients have died. The virus uses its spike proteins as adhesive factors that are pro-inflammatory for host entry through a specific receptor.

At present, NIAID also allowed the new vaccine to be fast-tracked into clinical trials. Once the genetic information of SARS-CoV-2 became available, the scientists quickly selected a sequence to express the stabilized spike protein of the virus in the existing mRNA platform.

In USA, the approving authority for vaccines is ‘Unites States Food and Drug Administration’ (USFDA)[5]. At the same time, FDA’s Center for Biologics Evaluation and Research (CBER) is responsible for regulating vaccines in the United States.

The steps in development of a new vaccine are as follows:

  • Exploratory stage
  • Pre-clinical stage
  • Clinical development
  • Regulatory review and approval
  • Manufacturing
  • Quality control

Among all above stages, the clinical development is the most time consuming and important affair. It is being conducted in three-phase process. New drugs must pass through these three phases of clinical trials before being deemed safe and effective for widespread use. Assuming the initial tests go well, it may be 12 to 18 months before this Coronavirus vaccine is ready for public use.

Phase 1

  • Phase 1 trials examine a small group of people, typically between 20 and 80 individuals, who receive different doses of an experimental treatment.
  • Over the course of several months, researchers monitor how each volunteer metabolizes the given treatment and what common side effects emerge in response to different doses.

Phase 2

  • Phase 2 trials typically examine several hundred people and monitor participants for periods of from several months to two years.
  • Primarily, Phase 2 trials serve as a secondary measure of safety and help researchers to refine the dosing of a particular medication.
  • At this stage, researchers select participants with characteristics, such as age and physical health that match those of the people who the vaccine is being developed for.

For example, although anyone can contract COVID-19, those of advanced age and those with chronic conditions are more likely to develop severe symptoms, so this could be a consideration in Phase 2 trials.

Phase 3

Phase 3 trials typically follow 300 to 3,000 volunteers over the course of one to four years. With a larger group of people, researchers can take note of unusual side effects of the drug, and by lengthening the study period, they can catch long-term side effects as they emerge. Phase 3 trials must demonstrate that a given drug provides the medical benefits it’s intended to; if this coronavirus vaccine passes that test, the FDA could approve the drug for widespread use.

Phase 4

Following approval by the FDA, drugs undergo Phase 4 clinical trials, otherwise known as ‘post-marketing surveillance trials’. Once a drug enters for public use, researchers monitor several thousand volunteers to spot side effects not seen in earlier trials and to track how well the vaccine works over extended periods of time.

The NIAID study aims to enroll a total of 45 healthy adults over a six-week time frame. The 45 volunteers in the new trial will receive varying doses of mRNA-1273, and be monitored over a 14-month period. Volunteers will receive two injections of the vaccine in the upper arm, with a 28-day gap between doses. The study, which is a Phase I trial, is meant to establish that the vaccine is safe and induces a desired response from participants’ immune systems. Proving that the vaccine is effective, there will be requirement of follow-up studies involving many more participants, which will take many more months.

 

[1] SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) Sequences, https://www.ncbi.nlm.nih.gov/genbank/sars-cov-2-seqs/ , accessed on March 19, 2020.
[2] First human trial for coronavirus vaccine begins Monday in the US, https://www.cnbc.com/2020/03/16/first-human-trial-for-coronavirus-vaccine-begins-monday-in-the-us.html , accessed on March 19, 2020.
[3] NIH Clinical Trial of Investigational Vaccine for COVID-19 Begins, https://www.niaid.nih.gov/news-events/nih-clinical-trial-investigational-vaccine-covid-19-begins ,  , accessed on March 19, 2020.
[4] Shanghai Fosun Pharmaceutical Co., Ltd., known as Fosun Pharmaceutical or just Fosun Pharma is a Chinese listed pharmaceutical company. It is majority owned by Fosun International. Fosun Pharmaceutical is the co-owner of Sinopharm Industrial Investment, the parent company of fellow listed company Sinopharm Group.
[5] Vaccine Testing and the Approval Process, https://www.cdc.gov/vaccines/basics/test-approve.html , accessed on March 19, 2020.
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