When it comes to the Covid-19 pandemic, the world is tracking data by the minute: the numbers affected, mortality rates, tests to confirm cases, and possible treatments, of course. However, the one news update that humanity is waiting for anxiously—and with billions of fingers crossed—is the approval of a vaccine, with the stamp of being safe and effective for use. The various bulletins on the progress of the vaccine are followed across the board, by individuals, governments, and bodies like the World Health Organization (WHO) which is tracking over 140 companies that are working independently, or in partnership with academia, in a relentless race to exit the pandemic.
The world is restless, but a vaccine was never built in a day.
Vaccine testing is a four-stage process (see box) and has historically taken between two to 12 years. Back in 2009, the H1N1—or swine flu—vaccine was an exception. It took only 93 days to start the clinical trial after identification of the vaccine candidate and it could be deployed while the epidemic was in progress. But that was possible because of the nature of the virus—the vaccine was similar to that used for regular influenza.
Closer to the standard time frame is the development of the Ebola vaccine, which was approved in 2019 by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (USFDA) long after the outbreak was over; the clinical testing had taken five years. Also the severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Zika viruses ended up being geographically localised, and the vaccines are still under clinical testing in phase 1.
However, recognising the havoc—and contagion—created by the Coronavirus, science and governments alike are trying to break the speed barrier with the Covid-19 vaccine. “The Covid-19 global pandemic has led to an unprecedented collaborative effort amongst industry, academia, regulatory bodies, and governments with huge financial investments,” says Amit Dinda, a professor in the department of pathology at AIIMS, and an executive council member at the Global Coalition of Regulatory Science Research.
In India, there are 21 manufacturers of human vaccines. Of these, Serum Institute of India, Bharat Biotech International Limited (BBIL), Zydus Cadila (the listed entity is called Cadila Healthcare), Biological E., and Dr Reddy’s Laboratories are in the Covid-19 vaccine fray, either through original research or partnerships, or both.
One of the lead players is the Adar Poonawalla-led Serum Institute, which is producing Covishield, the vaccine being developed by Oxford University and AstraZeneca. The vaccine platform, based on a chimpanzee adenovirus called ChAdOx, has begun phase 2 and 3 trials in the U.K., as well as phase 3 trials in Brazil, South Africa, and the U.S. Serum Institute is conducting phase 3 trials in India in 18 sites. According to interim data from AstraZeneca, the vaccine candidate is 70.4% effective, and is projected to be available in the first quarter of 2021. Serum Institute also has a manufacturing agreement with U.S. biotech company Novavax for its vaccine, NVX-CoV2373.
The other hopeful is Covaxin, the country’s first indigenous Covid-19 vaccine developed by the Indian Council of Medical Research (ICMR). Hyderabad-based BBIL has partnered with ICMR to take it through development and clinical trials. “The [BBV152] vaccine is derived from a strain of SARSCoV-2 (the Covid-19 virus) isolated by ICMR and the National Institute of Virology, Pune,” says Rajnikant Srivastava, director of Regional Medical Research Centre and head of research management, policy planning, and coordination at ICMR. BBIL has completed interim analysis of the phase 1 and 2 clinical trials and commenced phase 3 trials with 26,000 participants in India. They are pushing for a mid-2021 release of Covaxin, with ICMR asking 12 institutes to fast-track clinical trials.
Another indigenous candidate, Zydus Cadila’s ZyCoV-D, is currently in phase 2 of clinical trials and unlike other vaccines in development, this one doesn’t use live or dead viruses. Instead, it introduces plasmid DNA into the host cells, intended to transmit into the viral protein and create an immune response in the body. Explaining their choice of a DNA-based vaccine, Pankaj Patel, chairman, Zydus Cadila, says, “A clearly defined regulatory pathway for a DNA-based vaccine has been laid out by the USFDA and WHO.” He points out that DNA-based vaccines for SARS 1 and MERS-Cov had successful phase 2 trials even though they were subsequently not taken forward. Also, he says, “in case there is mutation in the Covid-19 virus, a modified vaccine can be produced within three months.” Patel points out that just creating a vaccine is not enough. Developers have to take it through the process of development, transportation, and distribution. “We found that a DNA vaccine is stable and suitable to be transported at 2-8 degrees [Celsius].”
Abroad, there’s the mRNA-based vaccine candidate BNT162b2, produced by BioNTech along with Pfizer and Fosun. Pfizer has claimed that the final results from its phase 3 trials have shown 95% efficacy. Moderna’s vaccine candidate, which is also mRNA-based, is another example. The American firm claims it has shown 94.5% efficacy. This vaccine candidate was prepared in 42 days for human trials once the genetic code of the virus was known. mRNA vaccines work by training the immune system to recognise a virus-like threat and begin producing antibodies to protect itself. While both candidates are yet to reach India, the vaccine race is heating up as there’s a pot of gold waiting for the winner.
Back home, also in the vaccine race is Dr Reddy’s Laboratories, which is conducting phase 2 trials with 100 volunteers before starting phase 3 trials to market Russia’s Sputnik V in India. Like the others, they also expect to get to market in the next few months. And most recently, Hyderabad-based vaccine-maker Biological E. got the go-ahead to conduct phase 1 and 2 clinical trials of the vaccine developed by U.S.-based Baylor College of Medicine. This makes it the fifth vaccine to go into human trials in the country.