The story so far: On April 23, Oxford University began a phase-1 human clinical trial of its vaccine – ChAdOx1 nCoV-19 – against a new coronavirus, SARS-CoV-2. A single dose of vaccine candidates will be given to 1,112 healthy volunteers to study safety, ability to produce an immune response and vaccine efficacy. Oxford University is optimistic about the positive results of vaccine candidates and has planned to get millions of vaccine doses before the end of the year even though the results of the final phase of the trial (phase-3) are awaited. The vaccine candidate was developed by the University Jenner Institute which began trials on humans on April 23 together with the Oxford University Vaccine Group.
How was the vaccine tested constructed?
The vaccine, ChAdOx1 nCoV-19, uses the common cold virus (adenovirus) which causes infection in chimpanzees. Adenovirus has been genetically altered so that it doesn’t grow after being injected. Its construction carries genetic material from new coronaviruses that make spike proteins. Surge proteins are found on the surface of the virus and play an important role in binding specific human receptors found on the cell surface and entering the cell.
By introducing genetic material from protein spikes, vaccine candidates will help the body recognize it and make antibodies against protein spikes. The antibodies produced will help improve the immune response and prevent the virus from entering human cells and causing infection.
Oxford University has used a vaccine made from adenovirus construction for more than 320 people and has found that it is safe and well tolerated. It does cause temporary side effects such as fever, headaches or diseased arms but is otherwise safe.
Has it been tested on animals?
The adenovirus construction has been used by Oxford University researchers to test the safety of the Severe Acute Respiratory Syndrome (SARS) 2002 and the Middle East Respiratory Syndrome (MERS). After the safety of the MERS vaccine was proven in trials conducted in the UK, the trial began in December last year in Saudi Arabia, where MERS outbreaks often occur.
Safety of vaccine candidates was previously tested on six rhesus monkeys.
A single dose protects all six animals for almost a month even when exposed to high levels of the virus, increasing the confidence of researchers.
How is the clinical trial process?
Up to 1,112 healthy volunteers from Oxford, Southampton, London and Bristol have been recruited for phase-1 trials. Volunteers, both men and women between 18-55 years old, are being recruited for the trial. A single dose of vaccine candidates will be given to volunteers. Participants will be randomly assigned to receive vaccine candidates (ChAdOx1 nCoV-19) or ‘control’, the MenACWY vaccine, for comparison.
Oxford University uses the MenACWY vaccine – which protects against four types of meningococcal bacteria – rather than copy control. The participants will not know whether he accepted the vaccine candidate or not. University researchers will also test two vaccine candidate doses given four weeks separately to a small group of 10 volunteers to assess the dose and immune response.
For the control group, why are vaccines for meningococcal bacteria used and not copy?
The MenACWY vaccine is a licensed vaccine given routinely to adolescents in the UK since 2015. The MenACWY vaccine is used as an “active control” vaccine to help understand participant responses to ChAdOx1 nCoV-19. The reason for using this vaccine, rather than copy control, is because researchers hope to see some small side effects of the ChAdOx1 nCoV-19 vaccine such as arm pain, headaches, and fever. Saline does not cause this side effect. If participants only receive this vaccine or copy control, and then develop side effects, they will realize that they have received a new vaccine. It is important for this study, said Oxford University, that participants remain blind to whether they have received the vaccine or not, “such as, if they know, this can affect their health behavior in the community after vaccination, and can lead to bias in research results” .
While all participants will be told how to reduce the risk of infection, it is necessary that participants who receive both the vaccine are exposed to the virus and some are infected. Only thus will it be possible to understand if the vaccinated group remains protected or not compared to the control group. For this purpose, keeping participants in the dark about the vaccine received makes a strong trial.
What is the schedule for the trial?
Phase-1 trials are expected to be completed by the end of May if transmission remains high in the community. Phase-2 trials can be completed in August-September. According to Suresh Jadhav, Executive Director of the Indian Serum Institute Pvt. Ltd., phase-2 and phase-3 trials can be combined if the phase-1 trial results are encouraging.
When will the Pune Serum Institute start making vaccines?
According to Mr. Jadhav, the company will start producing vaccines once phase-3 or phase-2 / phase-3 trials begin. If the last two stages of the experiment are combined they will start producing vaccines at the end of June and be ready with millions of doses by the end of the year. The company is confident that it will produce 60-70 million doses of vaccine by the end of this year. He said, “Because we will start making it when the final phase of the trial begins, we will have millions of vaccine doses ready when the trial ends.”
How much does it cost?
In a tweet on April 30, Oxford University said that they partnered with AstraZeneca to produce and distribute vaccines as quickly as possible. It was said that the vaccine would be available on a “not for profit basis for the duration of the coronavirus pandemic”.