The COVID-19 vaccine development round the world is going ahead in serious earnest. World’s top pharmaceutical companies are going head to head, throwing up their top scientists and technologists as well as investing large amounts of scarce resources, even when their businesses are in doldrums. The governments of various countries are also scrambling to get to the most promising candidate and at the same time hedging their bets simultaneously on a few rival companies.
What is pushing the whole world to this mad rush? The COVID-19, a strain of coronavirus, is the most vicious virus to ravage human species during the last 100 years or so. This virus has claimed more than 27.6 million positively identified infection cases and 898,000 deaths round the world. Needless to say, many more infections and many more deaths had gone unreported and unidentified.
The vaccine against this virus, as in all other viruses, has to go through certain internationally accepted and proven steps to ensure safety and effectiveness to the public. If any short-cut is made or any corners are cut, then the confidence of the public to accept this medicine or any future medicine will be seriously shaken.
Of the hundreds of potential COVID-19 vaccines now in development round the glove, six are in the final stages of testing. This final stage is known as phase three clinical trial. Each one of these vaccines had gone through phase one and phase two testing before reaching the final phase. Only compromise that was allowed to these vaccines because of the urgency of this medication that phase one and phase two were allowed to be combined and run concurrently. These phases had to show that they are safe (with only short-term side effects, if identified, and no unexpected serious effects) and they elicit an immune response. The third phase is the final stage before approval is offered.
Usually the phase three trial comprises, what is known as case-control study, which is primarily a statistical process. The case group receives the actual vaccine which is being tested and the control group receives placebo i.e. simple saline or vaccine against a different disease. The selection of case-control groups of sample requires careful consideration and vetting. These sample groups should favourably reflect each other in parameters like racial mix, age distribution, gender distribution, economic conditions, patterns of behaviour and social habits.
To demonstrate the efficacy of the vaccine, there must be significantly fewer cases of the target disease in the vaccinated group compared to the control group. Depending on infection rates of the disease, a phase three vaccine trial may involve thousands to even tens of thousands of people. The bigger the sample size, the more reliable would be the output. To be approved, vaccines need to demonstrate that they are safe and effective.
One of these is the vaccine that the University of Oxford is developing – known as Oxford vaccine. This vaccine has passed through phase one and phase two testing with flying colours and now undergoing phase three testing. The purpose of a phase three trial is to assess whether this vaccine-induced immune response is strong enough to actually protect people from COVID-19. The vaccine is designed to provoke a T cell response within 14 days of vaccination – when white blood cells attack cells infected with the SARS-CoV-2 virus – and an antibody response within 28 days – when antibodies are able to neutralise the virus so that it cannot infect cells when initially contracted.
In the Oxford vaccine clinical trial, five countries in five continents have been chosen – India, the UK, South Africa, Brazil and the US. Thus, a wide variety of rich and developing countries in different climatic conditions had been chosen. The vaccine is being evaluated in these regions and hence the result would give a generic output applicable to almost the whole world.
In the first instance, nearly 17,000 people in three countries – the UK, South Africa and Brazil – have received the vaccines, with half being in the control group. These people would then receive booster vaccination between one and three months after the first vaccination. Exactly the same procedure is followed for both case and control groups, so that the volunteers do not know whether they received actual or placebo dose against COVID-19.
The data will be analysed statistically for each country and the results will be scrutinised and assessed by the regulatory bodies. If the results are positive, then regulatory bodies will approve of the vaccine for general use. On the other hand, if the result is marginal then there may be requirements of further improvement in the quality of vaccine or further clinical trial. This will inevitably delay in the use of vaccine by the general public.
AstraZeneca, the firm partnering Oxford to develop the vaccine, is overseeing a scaling up of manufacturing in parallel with clinical testing so that hundreds of millions of doses can be available if the vaccine is shown to be safe and effective. India’s Serum Institute has already started manufacturing the University of Oxford/AstraZeneca vaccine candidate before clinical trials have even been completed. This is to avoid any subsequent delay if the vaccine is approved.
However, a spokesman for AstraZeneca told the Guardian newspaper in the UK that the trial had been stopped to review the “potentially unexplained illness” in one of the participants. The spokesman also stressed that the adverse reaction was only recorded in a single participant and said pausing trials was common during vaccine development.
Notwithstanding the technical issues involved in producing medicines, Donald Trump tarnished the world-wide efforts to produce vaccines with his political agenda of getting re-elected. He declared that the vaccines would be available two days before the US presidential election on 5 November and thereby implicitly and egregiously taking credit for producing COVID-19 cure under his watch!.
However, a group of nine vaccine developers has announced a ‘historic pledge’ to uphold scientific and ethical standards in the search for coronavirus vaccine. The group includes such giant pharmaceutical companies as Pfizer, Merck, AstraZeneca, Johnson & Johnson, BioNTech, GlaxoSmithKline, Moderna and Novavax. By their pledge, they asserted that no matter what the politically motivated pressure may be exerted on them, they will ‘always make the safety and well-being of vaccinated individuals their top priority’. Self-publicised egoistic egregious political leaders will come and go, but the pharmaceutical companies are here to stay to produce and serve the people.
– Dr A Rahman is an author and a columnist.