The World Health Organisation lists 160 vaccines currently in development at various stages of research and development. This makes it the biggest vaccine development effort in the history of mankind while a pandemic is still on, said the Indian virologist Shahid Jameel. Of these, 139 are currently in “preclinical evaluation” stages, which means that vaccine candidates are being tested on animals.
Two Indian vaccine candidates have cleared this stage and have received regulatory approval to move for the next stage – clinical trials – although the WHO document does not list Covaxin, the vaccine candidate the Indian government was pushing. When asked why this was the case, a WHO representative said in an email that the WHO had a list of “attributes and criteria [that] provide considerations for the evaluation and prioritization of COVID-19 candidate vaccines to be considered for further development by WHO”, but did not say which criteria Covaxin did not meet.
The WHO lists 21 vaccine candidates globally that are in the clinical evaluation stage.
This is the stage where vaccine candidates begin to be tested on humans. According to the WHO, in phase I clinical studies, initial testing of a vaccine is carried out in small numbers of healthy adults, “to test the properties of a vaccine, tolerability, and, if appropriate,
clinical laboratory and pharmacological parameters”, primarily to test if it will be safe to administer the vaccine.
Phase II trials involve larger numbers of subjects and are intended to test if the vaccine candidate does produce an immune response in subjects, and to once again test for safety. Phase III involves a large number of participants to fully assess the safety and efficacy of a vaccine candidate. In Indian clinical trials for a covid-19 vaccine, this number could potentially run into tens of thousands, WHO chief scientist Soumya Swaminathan said in a recent interview.
Of the 21 vaccine candidates listed by the WHO in clinical trial stages, two have reached phase III – the private Chinese company Sinovac’s trial of an inactivated vaccine in Brazil, and the British-Swedish drug company AstraZeneca and the University of Oxford’s viral vector vaccine that is in a Phase II/III trial in England and in Phase III trials in Brazil and South Africa. Both types of vaccines attempt to get the body to come up with an immune response to the coronavirus; an inactivated virus vaccine uses a weakened or inactivated version of the virus, while a viral vector vaccine uses a virus to deliver coronavirus genes into cells. The AstraZeneca/ University of Oxford vaccine candidate looks the most promising of all current candidates, Jameel said.
These candidates, however, remain just that – candidates. The failure rate for vaccines in development is very high. An analysis of all vaccine projects in development from 1998 to 2009 found that the average vaccine took 10.71 years to be developed from the preclinical phase, and had a market entry probability of 6%.
The Indian controversy over overly-optimistic timelines for the Bharat Biotech- ICMR (Indian Council for Medical Research) vaccine is not the only such controversy. The Phase III trials of the US-Based Moderna’s vaccine, part-funded by the US government, have been delayed as the company and the government argue about how to conduct trials.
Failures make vaccine development even more expensive. Over 3.7 billion USD have already been committed to finding a vaccine for covid-19, according to data compiled by Policy Cures Research, a global health think-tank.
The actual cost of getting an epidemic infectious disease vaccine from the preclinical stage to the early clinical safety and efficacy testing (phase 2a) is substantially lower, according to estimates by researchers from the Coalition for Epidemic Preparedness Innovations (CEPI). “Accounting for probability of success, the average cost of successfully advancing at least one epidemic infectious disease vaccine through to the end of phase 2a can vary from US$84–112 million ($23 million–$295 million range) starting from… preclinical,” CEPI researchers wrote in a study published in The Lancet.
The focus of manpower and resources on vaccine development for covid-19 is unparalleled, says Jameel, who is the chief executive officer of DBT Wellcome Trust India Alliance, a non-profit that funds research in health and biomedical sciences in India. For comparison, there are currently only 82 vaccine candidates still in active development for tuberculosis, according to the WHO.
If a covid-19 vaccine is developed before 2021, the speed will also be unprecedented. The oldest of the active tuberculosis vaccine candidate trials dates back to 2007. Even for ebola, the most recent vaccine approved for use by the WHO, phase I trials began in November 2014, and the drug got WHO approval for use in November 2019, a full five years later.
The Indian government’s claim that it plans to roll out a vaccine by August 15 has been debunked, but even if a vaccine is available by 2021, that will still be historic.
Rukmini S. is a Chennai-based journalist.