Serum Institute of India, Pune, will start manufacturing the vaccine the moment the Phase-3 trial begins. The company is confident of making millions of vaccine doses ready by the time the trial ends. The vaccine will be made available on a “not-for-profit basis”.
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 positive outcome of the candidate vaccine and so has planned to get millions of vaccines before the end of the year even as results of the final phase of the trial (phase-3) is expected.
The vaccine candidate was developed by the University’s Jenner Institute who began trials in humans on April 23 jointly with the University’s Oxford Vaccine Group.
How is the candidate vaccine that is tested constructed?
The vaccine — ChAdOx1 nCoV-19 — uses 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 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 surface and entering into the cells.
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 so produced will help mount an immune response and prevent the virus from entering the human cells and cause an infection.
Oxford University has used vaccines made using the adenovirus construct to over 320 people and found it to be safe and well tolerated. It does cause transient side effects such as a fever, headache or sore arm but is otherwise safe.
Has the candidate vaccine been tested on animals?
The adenovirus construct has been used by Oxford University researchers to test the safety for both 2002 SARS and MERS. Once the safety of the MERS vaccine was proven in a trial carried out in the UK, 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. A single dose of the vaccine 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 design of the trial?
Up to 1,112 healthy volunteers from Oxford, Southampton, London and Bristol will be recruited for the phase-1 trial. Volunteers, both males and females between 18-55 years, will be 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 or a control. Oxford university will not be using saline solution for the control arm but instead use another licensed vaccine — MenACWY — that protects against four strains of meningococcal bacteria. The participants will not know if he/she received a candidate vaccine or not.
At the start of the trial, Oxford University will 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.
Why is a vaccine for meningococcal bacteria used and not saline for the control group?
The MenACWY vaccine is a licensed vaccine given routinely to teenagers since 2015. Unlike saline, the MenACWY vaccine causes a few side effects including a fever and headache. Since the candidate vaccine is expected to cause similar side effects such a fever, headache and sore arm. While participants will easily know if they have received the candidate vaccine or a dummy if saline is used in the control arm, it becomes difficult when MenACWY vaccine is used.
The reason why Oxford University researchers preferred the MenACWY vaccine for the control group is to make sure the participants are unaware whether they received the candidate vaccine or not. Becoming aware of this crucial information might result in altered health behaviour following vaccination leading to a bias in the results of the study.
While all participants would be told how to reduce infection risk, it is necessary that participants in both arms are exposed to the virus and some participants getting 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 vaccine 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, Phase-2 and Phase-3 trial may get combined if the Phase-1 trial results are encouraging.
When will Serum Institute start manufacturing the vaccine?
According to Mr. Jadav, 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. “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,” he says.
How much will the vaccine cost?
In a tweet on April 30, Oxford University said it is partnering with Astra Zeneca 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”.