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Covid-19 vaccine: Search, progress

Oxford University is trialling the latest major candidate, adding to vaccines being investigated worldwide. What are these, and why is a vaccine vital while studies continue on drug and antibody alternatives?

Written by Abantika Ghosh | New Delhi | Updated: May 9, 2020 10:43:26 pm
Covid-19 vaccine: Search, progress A volunteer at trials, led by the University of Oxford, on the newly announced vaccine candidate against Covid-19. (Source: University of Oxford via AP)

A recent announcement by the University of Oxford that researchers there had started testing a vaccine against the novel coronavirus disease (Covid-19) has raised hopes. Over the last few weeks, there have also been somewhat conflicting reports about the performance of a drug candidate, remdesivir, while Israel has announced a breakthrough in another possible line of treatment, that with antibodies.

Here, we look at vaccine candidates around the world, including the one announced by the University of Oxford.

How do vaccines work?

These are biological products that, when introduced in the body, teach the immune system to identify a disease-causing pathogen and store in memory which fightback options are the most effective. Some vaccines are live pathogens, whose ability to cause harm has been muted but whose essential identifying features have been retained so that the body can learn to recognise it.

For example, the yellow fever vaccine is a live, weakened yellow fever virus; the BCG vaccine too is a live attenuated strain derived from an isolate of Mycobacterium bovis used widely as a vaccine for tuberculosis. The polio vaccine has the killed virus. Still other vaccines bank on teaching the body to identify the toxins released by the pathogen and act.

What are the other therapy options besides vaccines?

Various drug and therapy options are being tried around the world. Besides the global interest in the drug remdesivir, India has been talking about convalescant plasma therapy (in which the blood plasma of recovered Covid-19 patients, with antibodies, are transfused into the new patient); the Health Ministry has clarified it is a trial and not an approved treatment. Israel recently announced a “significant breakthrough” in development of monoclonal antibodies (those created from a single clone of cells) to treat Covid patients.

Vaccines are important because a lot of resources are saved in preventing a disease and not having to treat it. Vaccines have been key to the elimination of once dreaded diseases such as smallpox.

For Covid-19, a vaccine is of paramount importance at this stage. Until an effective treatment emerges, there are only two possible courses ahead: Either communities develop herd immunity (a painful process involving high rates of infections and deaths), or a vaccine is made available around the world at affordable costs.

What is the new vaccine for which tests have been announced?

It was originally intended for another coronavirus — the one that causes MERS. It has been developed at the Jenner Institute and named ChAdOx1 nCoV-19.

In a statement issued on April 23, the University of Oxford said: “ChAdOx1 nCoV-19 is made from a virus (ChAdOx1), which is a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees, that has been genetically changed so that it is impossible for it to grow in humans. Genetic material has been added to the ChAdOx1 construct, that is used to make proteins from the COVID-19 virus (SARS-CoV-2) called Spike glycoprotein (S). This protein is usually found on the surface of SARS-CoV-2 and plays an essential role in the infection pathway of the SARS-CoV-2 virus. The SARS-CoV-2 coronavirus uses its spike protein to bind to ACE2 receptors on human cells to gain entry to the cells and cause an infection.”

The idea is to teach the body to recognise the spike protein of the virus by first exposing it to ChAdOx1 nCoV-19. Thus when SARS-CoV2 enters the body, an immune response is mounted based on that recognition. “Vaccines made from the ChAdOx1 virus have been given to more than 320 people to date and have been shown to be safe and well tolerated, although they can cause temporary side effects, such as a temperature, headache or sore arm,” the statement added.

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There is also an India connection to the vaccine. The Serum Institute of India, one of the largest vaccine manufacturers in the world, is a partner for the production of the vaccine in preparation for the trials. In a statement, the company has said: “SII will be manufacturing the vaccine in anticipation of clinical trials succeeding by September-October in the UK. The vaccine will not be made available to the public in two-three weeks, as suggested in some media reports. Following that, SII has undertaken the decision to initiate the manufacture at their own risk. The decision has been solely taken to have a jump start on manufacturing, to have enough doses available, if the clinical trials work.”

What is the progress of trials?

The vaccine leapt straight to human trials for testing of efficacy because the safety had already been proven earlier, when it was being developed as an option against MERS.

For the trial, 1,102 participants will be enrolled across Oxford, Southampton, London and Bristol. They will be split into the vaccine arm and the control arm; the control will not be a placebo as is usually done, but another vaccine. This will be MenACWY , a vaccine licenced for use against a common bacteria that causes meningitis and sepsis.

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This is being done because ChAdOx1 nCoV-19 causes some side-effects such as headache and fever. Using a placebo such as saline control would not produce those same side-effects, thus the subject would know what he or she had received. “If participants were to receive only this vaccine or a saline control, and went on to develop side effects, they would be aware that they had received the new vaccine. It is critical for this study that participants remain blinded to whether or not they have received the vaccine, as, if they knew, this could affect their health behaviour in the community following vaccination, and may lead to a bias in the results of the study,” reads the Oxford statement.

How many other vaccine candidates are under investigation?

By some estimates, over 40 vaccine candidates are in various stages of development around the world. Until the Oxford announcement, one of the most promising candidates was believed to be one developed by Moderna, a biotechnology company, that is now into phase I clinical trials under the aegis of the US National Institutes of Health (NIH).

UNITED STATES: On March 16, the day the first participant was enrolled in the trial for the Moderna vaccine candidate, the NIH said in a statement: “A Phase 1 clinical trial evaluating an investigational vaccine designed to protect against coronavirus disease 2019 (Covid-19) has begun at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is funding the trial… The open-label trial will enroll 45 healthy adult volunteers ages 18 to 55 years over approximately 6 weeks. The first participant received the investigational vaccine today.” The trial is looking at the safety of the vaccine and its efficiency in actually generating an immune response.

According to a current report filed by Moderna with the US Securities and Exchange Commission, a “… commercially-available vaccine is not likely to be available for at least 12-18 months, it is possible that under emergency use, a vaccine could be available to some people, possibly including healthcare professionals, in the fall of 2020.”

HONG KONG: Another candidate vaccine is being tested by Hong Kong-listed biotech firm CanSino Biologics. Having started after the NIH trials, the company last week announced that phase I trials have been cleared and the vaccine is moving into phase II of the trial “based on the preliminary safety data of the Phase I clinical trial”. The results of that trial have not been made public.

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Like the Oxford vaccine, this too is an adenovirus-based vaccine. The double-blind, placebo-controlled study in 500 healthy patients will be done in association with researchers form the Academy of Military Medical Sciences’ Institute of Biotechnology.

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