All vaccines come with risk, but the time it takes to develop an effective vaccine does not affect its quality.
The covid-19 pandemic set off a global race to develop a vaccine to combat it but given the devastating impact of the pandemic, researchers have had to shorten the creation of such a vaccine while ensuring that no shortcuts are taken on safety.
The average time taken to develop a vaccine development is between 12 and 15 years, according to Cape Town-based non-profit organisation, Vaccines for Africa. A new covid-19 vaccine is, however, expected to become available for public use within a record 12 to 18 months since the World Health Organisation (WHO) declared the novel coronavirus a global pandemic on March 11 this year.
The full DNA sequence of the coronavirus, which causes covid-19, was made available by Chinese authorities in January 2020, making it possible for researchers around the world to develop a vaccine with a target antigen (a substance that causes the body’s immune system to produce antibodies to fight off a virus). A deoxyribonucleic acid (DNA) or ribonucleic acid (RNA)–based vaccine allows researchers to begin creating a candidate vaccine without growing the virus in a cell or egg culture – steps taken in explanatory and pre-clinical trial phases that ordinarily can last up to six years. According to Johnny Mahlangu, head of the National Health Laboratory Service (NHLS) and School of Pathology in the faculty of health sciences at Wits University, the use of RNA platforms hastens a vaccine’s development.
“The reason they [RNA and DNA] are so important is that they can be manufactured in the laboratory and you do not need to wait for weeks, months or years to grow the virus in an animal model. You can formulate the DNA and RNA [antigen] target and start the development of the vaccine. This is one of the main reasons the covid-19 vaccine has developed so quickly,” said Mahlangu.
In the clinical development stage, a candidate vaccine is tested on humans. Phase one involves small-scale trials on 20 to 80 healthy adult participants. These trials are aimed at confirming whether the candidate vaccine is safe to use on humans and what immune response it raises.
Phase two trials are larger, involving several hundred participants, and continue to test the safety of the candidate vaccine and whether it evokes the desired immune response. Phase two trials also identify side effects, dosages and dosage schedules.
Phase three trials are carried out on a large scale, with thousands to tens of thousands of participants drawn from a range of population variables. These trials are the final test of the candidate vaccine’s efficacy. Across the globe there are currently nine covid-19 candidate vaccines undergoing phase three of clinical trials. There are 14 in phase two and 25 in phase one.
Wits University has partnered with the University of Oxford to run the Ox1CoV-19 vaccine trial, commonly referred to as the Oxford trial in South Africa. The process began on June 24 and phase three trials are now under way. Wits University is also leading the covid-19 Novavax vaccine trial, which started on August 17 and is undergoing phase two trials.
Professor Martin Veller, dean of the faculty of health sciences and participant in the Oxford trial, explained to Wits Vuvuzela that phase three trials are the most important part of the process.
“Phase three is always the most important because it is really where the true efficacy [of the vaccine] is demonstrated,” he said.
Clinical trials can run for five to nine years before a candidate vaccine is submitted for approval to a national regulatory agency.
“These things [clinical trials] take years, but you do not have the opportunity in infectious pandemics,’’ said Veller. ‘‘Frankly, the testing has to be accelerated.”
There are ways in which testing can be accelerated. According to Mahlangu, the time spent on clinical trials can be reduced: “The clinical trial process is a mechanism ensuring that the vaccines are safe. They comprise a sequence of steps. One could overlap some aspects of phase two and three.”
Mahlangu said researchers could embrace an adaptive trial design, a method that enhances the clinical trials’ flexibility and reduces time, which allows researchers to respond to results immediately.
“This is an accepted way of doing clinical trials,’’ he said. ‘‘In the context of covid-19, an adaptive trial design is one way to compress the time period.”
Another way to shorten clinical trials is by “matching vaccine development to where the disease is prevalent. Developing a vaccine that matches the evolution of the disease allows vaccine development to be faster,” Mahlangu added.
If the candidate vaccine passes the third phase, the manufacturer submits all data and applies to the relevant regulatory authority for a license to market the product. In South Africa the South African Health Products Regulatory Agency (SAHPRA) is the entity that regulates all medical products.
Safura Abdool Karim is a senior researcher and public health lawyer at the Wits University School of Public Health and the South African Medical Research Council’s Centre for Health Economics and Decision Science. Karim said in an article published in September by Africa Check that “without SAHPRA registration, a health product cannot be prescribed, sold or even advertised”.
Mahlangu also told Wits Vuvuzela large amounts of data are submitted for review and this can be time-consuming. The process can, however, be fast-tracked without compromising safety if researchers facilitate effective data submissions during pre-clinical and clinical trials.
“One area that can never be compromised is that of safety and quality. If there is any impact on the safety and quality of the vaccine, it is unlikely it [the vaccine] will ever be approved. There might be a compression of the timelines when it comes to data collection, but no vaccine will ever be allowed unless it has undergone regulatory review and approval,” said Mahlangu.
According to the same Africa Check article, if a covid-19 vaccine is made available overseas it will undergo regulatory checks by another regulatory agency before SAHPRA. If the vaccine’s use is approved internationally, SAHPRA can expedite its approval, which could take one to two years.
If a candidate vaccine from the Oxford or Novavax trials passes all clinical phases, the data will have to undergo regulatory evaluation in each participating country before its use is approved in South Africa.
So can we trust a rapidly produced covid-19 vaccine? Yes – but only if all the evidence is available and risks are clearly identified. Kick-off of the covid-19 vaccine benefited from already existing RNA platforms, which allowed researchers to skip years of pre-clinical trials. The global demand for a vaccine has also allowed certain regulatory measures to be condensed and increased flexibility to be granted to researchers.
FEATURED IMAGE: Viroshnee Matadin, a registered nurse at a Medicare Health pharmacy in Johannesburg, demonstrates how a flu vaccine is administered. Photo: Laura Hunter
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