Bharat Biotech’s Covaxin: key facts as India races towards a covid-19 vaccine

When Bharat Biotech’s covid-19 vaccine candidate Covaxin received the Drug Controller General of India’s go-ahead to begin human trials recently, there was a sense of optimism. But a letter on 2 July from the Indian Council of Medical Research (ICMR) left the scientific community in a tizzy. “It is envisaged to launch the vaccine for public health use latest by 15th August 2020 after completion of all clinical trials," the letter said. ICMR followed this up with a clarification on 4 July that the letter was meant “to cut unnecessary red tape, without bypassing any necessary process, and speed up recruitment of participants".

In normal circumstances, the development of a vaccine takes years, not days or months. Vaccine development is also an expensive proposition. In a recent article for The New York Times, veteran personal health columnist Jane E. Brody cited the original roll-out of the Salk polio vaccine in 1955 as a reminder of how the premature release of a vaccine can cause more damage than good. “A mishap in mass-producing the vaccine caused polio in 70,000 children, permanently crippling 164 of them and killing 10," she writes.

We look at some key questions related to the development of Covaxin, and whether or not it is scientifically (and ethically) possible to achieve it in a short span.

What is Covaxin?

Bharat Biotech’s Covaxin is an indigenous, inactivated vaccine that is being developed in collaboration with ICMR’s National Institute of Virology (NIV), Pune. According to the company, Covaxin has been developed from an Indian strain of the novel coronavirus, which was isolated by NIV.

What is an inactivated vaccine?

Inactivated vaccines are made from microorganisms (these could be viruses, bacteria, etc.) that have been killed through physical or chemical processes. According to a World Health Organization (WHO) module on different types of vaccines and their adverse effects, these killed organisms “cannot cause disease".

“Inactivated vaccine as a platform for vaccine preparation is one of the oldest ones. Essentially, for a viral vaccine, you take the virus and you kill or inactivate it—in the sense that the ability of the virus to divide and reproduce itself is completely taken away, which is how the virus would survive otherwise in the host," says immunologist Vineeta Bal, part of the visiting faculty at the Indian Institute of Science Education and Research, Pune. “The immune system normally uses proteins, lipids, carbohydrates, etc., to mount an immune response. So while the inactivated virus cannot multiply, it can still trigger a response through these components," she adds.

What are the other platforms to develop the vaccine?

There are multiple platforms that are being developed to produce a covid-19 vaccine: viral-vectored, protein subunit, live attenuated. But the most promising amongst them are DNA- and RNA-based platforms, which leverage the nucleic acid component. According to a paper published in The New England Journal Of Medicine in May, RNA and DNA vaccines can be made quickly because they require no culture or fermentation, relying instead on synthetic processes. But there are no RNA-approved vaccines so far.

Is it scientifically possible to develop a vaccine so quickly?

“In a straightforward answer, no," says Bal. There are a minimum of three levels within the human trials for a vaccine itself. And Bal explains how it is absolutely critical for these three levels to show positive results for the vaccine to be ready for public use. Any premature release of a vaccine can also result in potential side effects. “If phase 1 and phase 2 (of the trials) are done haphazardly, then we do not know in the first instance if the vaccine is safe. The vaccine’s ability to generate an immune response of the desired kind is another major limitation. Every vaccine does not provide what we immunologists describe as ‘protective immunity’," adds Bal. Another key factor is the duration of this protective immune response. “If this protective immune response is disappearing in four weeks, it doesn’t work. For a vaccine, we don’t want such a short protective phase," she adds.

The ethics of it

The timing and tonality of ICMR’s initial letter has also raised some questions on the ethics surrounding vaccine development. In a series of tweets on 3 July, public health and bioethics researchers Anant Bhan pointed out: “To my knowledge, such an accelerated development pathway has not been done EVER for any kind of vaccine, even for the ones being tried out in other countries. Even with accelerated timelines, this seems really rushed, and hence with potential risks, inadequate attention to process." Speaking over the phone, Bhan explains how the one thing that is clear about vaccine research is that the chances of success can be fairly low. “HIV is a good example. We still don’t have a vaccine for it," says Bhan. “I think presupposing or being able to pre-fix a launch date (for the vaccine) doesn’t really add up. You can try to expedite things but unless you follow the proper protocols and procedures, it is not going to be possible to ensure that you have something which you are completely sure about, in terms of the data that you have produced," he adds.

Some important numbers on efforts around the world to find a covid-19 vaccine

4: The number of years it took Dr Maurice Hilleman to develop the mumps vaccine in 1967. He used a swab from his daughter’s throat in March 1963 to isolate the virus. Mumpsvax was developed and licensed in record time and played a key role in the early battle against the contagious illness.

10.71: The average number of years it takes for the development of a vaccine, according to a 2013 study published in peer-reviewed scientific journal PLOS One.

18: The total number of vaccines that are in clinical evaluation around the world. This is according to a draft landscape of covid-19 candidate vaccines released by WHO on 2 July. Around 129 vaccine candidates are in the preclinical evaluation stage.

145: The number of covid-19 vaccines that are being developed by researchers globally, according to The New York Times coronavirus vaccine tracker. The tracker also estimates that 21 vaccines are in human trials.