Covid-19: Decoding the global search for a vaccine
There is progress. But it is crucial to follow the best regulatory and ethical practices, even if it takes time
Finding a vaccine for Sars-CoV-2 has become the single-point agenda for the global scientific fraternity. No other disease has seen such unwavering focus in recent memory. The public believes — and rightly so — that the pandemic will only be curtailed once an effective vaccine becomes available.
How many vaccines are currently being tested? As per the World Health Organization (WHO), there are at least 28 coronavirus vaccines in clinical trials around the world, including four that have successfully completed the phase 2 expanded safety trials. These have now entered phase 3 for wider testing and assessing effectiveness. Another 150-plus are in the early stage of development.
Vaccines are an article of faith for all of us because they have eradicated diseases that have ravaged humanity for millennia. The reason why vaccines are safe, and may perhaps be the most effective exit strategy from an infectious pandemic, is because they have generally undergone years, if not decades, of intensive research and development. The fastest vaccine ever developed is the one for mumps, and even that took over four years.
However, with Covid-19, time is a luxury we can ill-afford. Even so, the major companies still estimate a minimum of 12-18 months before a vaccine will be ready for manufacture. But so far, the prospects look bright although it will be a heroic act if even this timeline is achieved. It is equally possible that the effectiveness level of the best of the vaccine(s) may not be as high as one would desire.
Researchers have used many different methods for making proteins that are a “lookalike” of the S protein of the original virus, but have the ability to trigger the immune system of the host to induce both a neutralising antibody and a memory T-cell response.
Because vaccines eventually have to be administered to billions of healthy people, the path to their development is often vigorous and time-consuming. The need to perform extensive animal studies to ensure the safety and effectiveness of the product, prior to the extended human trials, cannot be overstated. Further, careful monitoring is needed to document evidence of any undesirable side effects.
Of the several trials underway, a few are real front-runners. One is the vaccine, called ChAdOx1 designed by Oxford University and developed by AstraZeneca. Made from a genetically-engineered virus that causes the common cold in chimpanzees, it has been heavily modified such that it cannot cause infection in humans. Published results on the phase 1/2 randomised-controlled trial of this vaccine involving 1,077 volunteers from ages 18 to 55 in the United Kingdom are promising so far. However, it is too early to ascertain whether it is safe enough to offer protection.
Phase 3 trials of this vaccine involving variable age groups among different ethnic groups in several countries are underway. There are other potentially viable candidates, including Sinovac from China and BioNtech Pfizer from Germany, both of which have entered phase 3 trials.
Another vaccine that has shown promise is the one being developed by the US Biotech firm, Moderna, based on a messenger ribonucleic acid (mRNA) platform. Labelled as the mRNA-1273 vaccine, it has revealed a good safety profile in all volunteers who received high doses. Crucially, the 100 microgram dose group elicited high neutralisation antibody and robust memory T-cell responses. This vaccine has also entered the crucial phase 3 trial stage.
India, with its world-class manufacturing hubs, is a powerhouse of vaccine production. About half of the vaccine requirements of the world are met by India. The Pune-based Serum Institute of India is partnering with AstraZeneca to produce bulk doses of its vaccine and has also received the Drug Controller General of India’s permission to conduct phase 3 trials on over 1,400 volunteers from India.
Besides, at least seven indigenous candidate vaccines are under various phases of trial in India, of which two, namely Bharat Biotech and Zydus-Cadila, have already entered phase 1 trials after successful pre-clinical testing.
The critical aspect of the process is to develop a protein that must be close to the original virus, and against which the body is able to raise antibodies for neutralising the virus. Any deviation could lead to the development of “blocking factors” through a process called Antibody Dependent Enhancement (ADE).
Simply put, rather than neutralising the virus, such antibodies could do the opposite, namely facilitate further virus entry into cells. This has happened earlier for the dengue virus where the vaccine, rather than conferring protection, actually acted like a silent primary infection.
Recently, the Indian Council of Medical Research organised an international symposium to discuss novel ideas in science and ethics of vaccines against Covid-19. Most speakers highlighted the need for adopting best regulatory and ethical practices even at the cost of speed, full compliance of human rights and above all, the need to develop policies and procedures for “equitable access”, should an effective vaccine become available, possibly before next summer.
Until an appropriate vaccine becomes available as the exit strategy for Covid-19, people must also contribute and help the health authorities slow the spread of the virus. Adopting simple habits in day-to-day life such as social distancing, mask-wearing whenever in public places and regular hand-washing would go a long way in controlling the infection.