Earlier this week, Bharat Biotech announced that it had developed a vaccine against the novel coronavirus, named Covaxin, together with the Indian Council of Medical Research (ICMR) and the National Institute of Virology (NIV), Pune. The company had also received permission from the Drug Controller General of India (DCGI) to begin human trials, expected to commence in August.

On Thursday, the ICMR’s Balram Bhargava said in a letter to Bharat Biotech, “It is envisaged to launch the vaccine for public health use latest by 15th August 2020 after completion of all clinical trials.”

Bharat Biotech is a reputed drug manufacturer that delivers four billion doses around the world for infections like rotavirus, hepatitis, Zika, Japanese encephalitis and others. However, its claim that Covaxin is indigenous – advanced, among others, by managing director Krishna Ella – raises some doubts.

According to Bharat Biotech, Covaxin is an inactivated vaccine developed from an Indian strain of the novel coronavirus isolated by NIV. No further information has been provided, especially about the nature of the vaccine or how it was developed. There have been no prior announcements either about when the process of developing such a vaccine was begun.

ICMR transferred the strain NIV had isolated to Biotech Bharat on May 9. The company published its press release on June 29. So there were only 50 days in between, during which time the company should have developed the inactivated vaccine, conducted preclinical animal trials (with mice and hamsters, according to the company), and sent its reports to be evaluated and approved by DCGI.

Although ICMR had promised to expedite the process, animal trials with mice typically take at least three months to conclude. Krishna Ella said as much in an interview on April 7: “It will take at least three months to do animal trials to establish the safety properly.”

A related issue is that animal trials for COVID-19 can only be conducted with hACE2 transgenic mice, as ‘normal’ mice can’t get infected with the novel coronavirus. These mice need to be shipped from the US, Europe or China, which Ella has also acknowledged.

These issues therefore raise concerns about whether Bharat Biotech could really have proceeded to the human-trials phase of vaccine development within only 50 days of receiving the inactivated virus from NIV.

Collaboration with US company
There is an alternative, and admittedly speculative, explanation for the vaccine’s provenance.

Bharat Biotech has currently invested in two other vaccines: CoroFlu in collaboration with FluGen Inc. and the University of Wisconsin-Madison, and an inactivated rabies vaccine vehicle for coronavirus proteins developed along with Matthis Schnell, director of the Jefferson Vaccine Centre (JVC), Pennsylvania. The latter is of interest.

On May 20, Bharat Biotech announced its collaboration with JVC as well as the license it had received to conduct clinical trials, and to produce and deliver vaccines in 80 countries excluding the US, Europe and Japan. On April 7, JVC announced a promising vaccine candidate named Coravax.

Coravax uses an inactivated rabies vaccine to carry the spike protein of the novel coronavirus. The spike protein attaches to a host cell and causes an infection, so experts expected this vaccine to trigger a good immune response on the body’s part. Schnell corroborated this response following preliminary tests with animals. Schnell added that JVC would need one more month to complete follow-up studies.

Using a rabies vaccine to deliver a vaccine for the novel coronavirus is a bit of technology that researchers perfected for use against the MERS and SARS viruses as well. And it’s possible that Bharat Biotech’s Covaxin uses the same technology.

In early 2019, Bharat Biotech acquired Chiron Behring Vaccines Pvt. Ltd. from GlaxoSmithKline and ramped up production of the rabies vaccine Chirorab to 15 million units a year. So the company already has the ability to mass-produce this vaccine.

Bharat Biotech hasn’t shared any technical details of Covaxin. But based on what we already know, there appears to be room for the possibility that Covaxin is Coravax by another name – and by another viral strain. And even if the vaccine is wholly indigenous, the timelines for the animal trials don’t line up. The Wire Science has written to Dr Krishna Mohan of Bharat Biotech, and this article will be updated when he responds.

PREM ANAND MURUGAN
The Writer is a PhD student at IIT Kanpur.

Courtesy Science The Wire