The story so far: On April 23, Oxford University initiated a phase-1 human clinical trial of its vaccine — ChAdOx1 nCoV-19 — against the novel coronavirus, SARS-CoV-2. A single dose of the candidate vaccine will be administered to 1,112 healthy volunteers to study the safety, ability to produce immune response and efficacy of the vaccine. Oxford University is optimistic of a positive outcome of the candidate vaccine and has planned to get millions of doses of the vaccine before the end of the year even as results of the final phase of the trial (phase-3) are awaited. The vaccine candidate was developed by the University’s Jenner Institute which began trials in humans on April 23 jointly with the University’s Oxford Vaccine Group.
How was the vaccine being tested constructed?
The vaccine, ChAdOx1 nCoV-19, uses the common cold virus (adenovirus) that causes infections in chimpanzees. The adenovirus has been genetically altered so that it does not grow once injected. The construct carries the genetic material of the novel coronavirus that makes the spike protein. The spike protein is found on the surface of the virus and plays a crucial role in binding to specific human receptors found on cell surfaces and entering the cells.
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By introducing the genetic material of the spike protein, the candidate vaccine will help the body recognise it and make antibodies against the spike protein. The antibodies produced will help mount an immune response and prevent the virus from entering the human cells and causing an infection.
Oxford University has used vaccines made from the adenovirus construct to over 320 people and has found it to be safe and well tolerated. It does cause transient side effects such as a fever, headache or a sore arm but is otherwise safe.
Has it been tested on animals?
The adenovirus construct has been used by Oxford University researchers to test safety for both the 2002 Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Once the safety of the MERS vaccine was proven in a trial carried out in the U.K., a trial began in December last year in Saudi Arabia, where MERS outbreaks occur frequently.
The safety of the candidate vaccine was earlier tested on six rhesus macaque monkeys.
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A single dose protected all the six animals for nearly a month even when exposed to high levels of the virus, boosting the confidence of the researchers.
What is the process of the clinical trial?
Up to 1,112 healthy volunteers from Oxford, Southampton, London and Bristol have been recruited for the phase-1 trial. Volunteers, both male and female between 18-55 years, are being recruited for the trial. A single dose of the candidate vaccine will be administered to volunteers. The participants will be randomly assigned to receive either the candidate vaccine (ChAdOx1 nCoV-19) or a ‘control’, the MenACWY vaccine, for comparison.
Oxford University is using the MenACWY vaccine — that protects against four strains of meningococcal bacteria — rather than a saline control. The participants will not know if he or she received a candidate vaccine or not. The university researchers will also be testing two doses of the candidate vaccine given four weeks apart on a small group of 10 volunteers to assess the dosage and immune response.
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For the control group, why is a vaccine for meningococcal bacteria being used and not saline?
The MenACWY vaccine is a licensed vaccine given routinely to teenagers in the U.K. since 2015. The MenACWY vaccine is being used as an “active control” vaccine to help understand participants’ response to ChAdOx1 nCoV-19. The reason for using this vaccine, rather than a saline control, is because researchers expect to see some minor side effects from the ChAdOx1 nCoV-19 vaccine such as a sore arm, headache and fever. Saline does not cause any of these side effects. 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 the study, says Oxford University, 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”.
While all participants will be told how to reduce infection risk, it is necessary that participants receiving both vaccines are exposed to the virus and some get infected. Only then will it become possible to understand if the vaccinated group remained protected or not compared with the control arm. For this purpose, keeping the participants in the dark about the vaccine received makes the trial robust.
What is the timeline for the trial?
The phase-1 trial is expected to be completed in end-May if transmission remains high in the community. The phase-2 trial may be completed by August-September. According to Suresh Jadhav, Executive Director of the Pune-based Serum Institute of India Pvt. Ltd., phase-2 and phase-3 trials may get combined if the phase-1 trial results are encouraging.
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When will Pune’s Serum Institute start manufacturing the vaccine?
According to Mr. Jadhav, the company will start manufacturing the vaccine the moment the phase-3 trial or the combined phase-2/phase-3 trial begins. If the last two stages of the trial are combined then it would start manufacturing the vaccine by end-June and be ready with millions of doses by the end of the year. The company is confident of manufacturing 60-70 million vaccine doses by the end of the year. He says, “Since we will begin manufacturing when the last phase of the trial is initiated, we will have millions of vaccine doses ready by the time the trial ends.”
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How much will it cost?
In a tweet on April 30, Oxford University said it is partnering with AstraZeneca to manufacture and distribute the vaccine as quickly as possible. It said the vaccine will be made available on a “not for profit basis for the duration of the coronavirus pandemic”.