Oxford vaccine trial step in right direction, but challenges still ahead
- A preliminary trial of Oxford's coronavirus vaccine candidate showed positive results
- However, we need to await trial results from other countries, including SA and Brazil
- The Oxford team is also moving on to 'challenge trials', which local experts say are warranted
Earlier this week, Health24 reported on the latest development in the Oxford coronavirus vaccine trial that began in April. Preliminary results, published in The Lancet, showed that the vaccine, named AZD-1222, triggered a positive immune response in participants and indicated no early safety concerns.
Although the results so far are promising, we still have a long way to go. Health24 spoke to Honorary Professor Robert Wilkinson from the Institute of Infectious Disease and Molecular Medicine (IDM) at the University of Cape Town (UCT), and Director of The Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa); and Professor Thomas Scriba, Deputy Director of Immunology and Laboratory Director at UCT, about the steps ahead.
Results a step in the right direction
The recently published results are a positive breakthrough, no doubt, but is it too early to get excited about the possibility of a vaccine? Well, it depends on how you look at it.
“The fact that there were no serious adverse events recorded in this trial is definitely a positive result and an exciting one," said Scriba, adding: "Of course, we shouldn’t get ahead of ourselves and think that this [vaccine] is ready to be rolled out. That’s not the case. But it’s an important step forward.”
It’s also critical that the testing is done in other countries with diverse population groups, so that the results can accurately represent the population group, and so that we know it’s safe to be used in these groups, explained Scriba. South Africa, Brazil and the US are also currently running trials, with results in SA expected as early as November, Health24 recently reported.
Wilkinson added: “The results show that there’s an immune response to the vaccine and that’s not discouraging. But we’ve been down this road before.”
Wilkinson's main experience has been with tuberculosis (TB) vaccines, and he explained that there have been a number of trials that elicited a positive immune response, but in the end didn’t show any efficacy.
“It’s been the same story with HIV vaccines as well. The NIH had to stop a trial just this year where the rationale behind it was very solid; the immune responses were all right – but it just didn’t work at all,” said Wilkinson, adding that the results of the Oxford Phase I/II trial are good and are what scientists would have wanted, but that, while the findings are promising, we need to await the larger trial results.
Shabir Madhi, Professor of Vaccinology at the University of the Witwatersrand (Wits) in Johannesburg, who is leading the leading the SA trial, also commented on the results during an ECN Africa webinar this week:
"The Oxford data that was published were really exciting; it (the AZD-1222 vaccine) probably shows the most robust of immune responses compared to, for example, the Moderna vaccine, but that does not necessarily prove that the vaccine would actually protect against Covid-19."
Developing a vaccine at breakneck speed
Many people have been particularly concerned about the rapid pace at which this potential vaccine is developed. Under usual circumstances, vaccine development can take a number of years before it is deemed effective and rolled out to population groups. In this case, however, developing a vaccine at breakneck speed is arguably justifiable, given that thousands of people worldwide are dying because of Covid-19, said Scriba, also pointing to the risks involved:
"On the other hand, that breakneck-speed development of a vaccine could come with potential safety issues that are overseen, and that maybe would’ve been detected if the vaccine would’ve taken many years under much more careful development. Having said that, this is not a completely novel technology being used for this vaccine. A lot is already known about it, and so that certainly helps to accelerate the development."
Scriba also explained that considering the high Covid-19 mortality rates, ultimately decisions have to be made about whether to accelerate some of the safety assessment steps that would potentially detect something rare that may happen in one in a thousand, or one in a million individuals who do receive the vaccine.
No shortcuts being taken
"I should also emphasise that the typical independent safety monitoring processes and external audits that apply to clinical trials, which are incredibly rigorous and conservative, are in place in these Covid-19 vaccine trials – it’s just all accelerated," said Scriba.
"The rigour with which medical interventions, such as vaccines, are developed require many layers of oversight and accountability and the safety data are reviewed by independent boards of expert doctors, ethics committees, health product regulators and external reviewers and monitors.
"None of these steps and processeshave been removed – it’s just that everyone works overtime to make the review process the highest priority so thatdecisions can be reached much faster."
Wilkinson iterated this in saying that what we're seeing is essentially "the usual process being sped up very quickly", and that it's being done because of the urgency of the situation.
"What we’re seeing here is acceleration of the usual routine process on the basis of urgency, but I don’t see evidence of shortcuts being taken," he said.
Oxford team moving into challenge trials: is this ethical?
Earlier this week, The Guardian reported that the team behind the Oxford Covid-19 vaccine is aiming to begin "challenge trials" which will involve volunteers being intentionally exposed to the virus in a controlled laboratory setting – a controversial move as there is no proven cure for Covid-19 yet.
Although human challenge trials, in an attempt to design a vaccine, are not new, doing it all depends on how easy you are able to deal with the infection, said Wilkinson.
“It’s fairly common in testing vaccines for malaria. Malaria is a life-threatening disease, but there are also very good treatments, so a human challenge becomes much easier in that case. Human challenges with HIV, for instance, are impossible because the disease has lifelong consequences and can’t be eradicated.”
If the challenge trials were to happen, Wilkinson explained that a particular group of volunteers will be included in the study, i.e. healthy, young individuals who are at low risk of contracting Covid-19.
Scriba added: “I’m sure they’d select an extremely tight, small group of individuals who are highly unlikely to develop severe disease. They will be monitored very carefully. I don’t know what the protocol looks like, but given that it’s a pandemic and international emergency, it may be possible to make a case for doing such a challenge study.”
However, this type of trial comes with its own set of problems, explained Wilkinson, in that if it does prove efficacious, that doesn’t necessarily tell us that it’s going to work in the population of interest, which is people above the age of 50.
For this reason, and in this context, trials involving natural infection, which are the ones currently happening, are favoured over the challenge trials. However, because challenge trials can be completed in a short period and require far fewer people, we can expect the possibility of it happening, said Scriba.