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Infectious Diseases

Updated 30 June 2020

SA's vaccine trial: Covid-19 science is moving fast, what about safety?

On the topic of the risks and safety of the new SA Ox1Cov-19 vaccine trial that started this week, Professor Shabir Madhi said that the safety of participants will be ensured.

  • The first African Covid-19 vaccine trial started in South Africa this week
  • The study will include 2 000 volunteers
  • Professor Shabir Madhi spoke about ensuring the safety of volunteers during the course of the study

The South African Ox1Cov-19 Vaccine VIDA-Trial is the first clinical trial in Africa for a Covid-19 vaccine and is currently underway. Although more than 100 vaccines are in development, this one, named ChAdOx1 nCoV-19, is one of only six studies involving humans, said Professor Shabir Madhi, professor of vaccinology at the University of the Witwatersrand (Wits) in Johannesburg, during a virtual press conference hosted by Wits, Health24 reported. Madhi is also leading the SA study.

On the topic of whether it's ethical to experiment on humans for a disease that remains poorly understood, Madhi explained the following at a MyHealthTV.com webinar on Wednesday.

Vaccine development generally takes a number of years before a vaccine is made available to the public. How, then, can this trial expect results in one to two years?

Madhi explained that although it takes, on average, between five and 10 years to develop a vaccine, in this instance scientists are trying to condense this into a one to two year period. Madhi does not ignore the risks associated with this, but clarifies:

“It does come with some risks and we can’t understate that risk. But, at the same time, these studies are being done under intense regulatory oversight, as well as oversight by independent scientists who form part of a data and scientific monitoring committee which basically interrogates all the serious adverse events that occur in the study, and make a conclusion as to whether those adverse events are possibly related to the vaccination or not.”

In the Wits briefing on Tuesday, Madhi commented that ongoing evaluation of safety by the Independent Data and Safety Management Committee will be part of the study and that if there’s any concern on the committee’s part, the study will be terminated immediately.

Madhi also explained that common side effects such as pain at the site of injection or developing a transient fever for a few hours per day are expected, as this is simply a manifestation of the immune response to the vaccine in individuals, which happens with most vaccines that are administered.

“Those are the realities around vaccines but those are self-limiting, and in terms of the risk-benefit profile, the benefits of being vaccinated against life-threatening diseases far outweighs what are essentially self-limiting adverse events,” he commented. 

Will the volunteers be exposed to the SARS-CoV-2 virus after being administered with the vaccine?

This usually happens in 'challenge trials' that involve animals, where some are vaccinated and others aren’t, after which they’re then challenged artificially with the virus to investigate whether the vaccine protects them against developing the disease.

However, this won’t be done in the SA Ox1Cov-19 vaccine trial. Although human challenge studies are also commonly done, this can only happen when a treatment for the disease is already available. Since we don’t have any Covid-19 treatment yet, this method cannot be undertaken. Madhi explains:

“Rather, because of the natural evolution of the outbreak, people will, unfortunately, get infected in South Africa and that’s going to be an ongoing thing – irrespective of whether you participate in the study or not. Unfortunately, there’s no tool that we’ve got that’s 100% foolproof in preventing people from getting infected.”

Madhi further explained that since people will be exposed to the virus naturally, it is without question that some will end up being infected with Covid-19. This means that in the group of 2 000 enrolled volunteers, some will become infected, but this would have occurred independently of their participation in the study.

However, what the research team will be comparing is the difference in infection rate between the two groups: the group that received the vaccine, and the group that received the placebo (a saline injection).

Could the ChAdOx1 nCoV-19 vaccine actually cause Covid-19 in participants?

The short answer is no, said Madhi. Instead, the vaccine aims to protect against Covid-19, and whether it protects against all forms of severity of the disease must still be seen. Madhi explained that different technologies are used to develop vaccines, and the technology that was used to develop ChAdOx1 nCoV-19 is what is known as a "non-replicating vector-based vaccine".

It uses adenoviruses, which are a group of common viruses that commonly causes fever, coughs, and sore throats, for instance, and have been with us for decades. However, Madhi added that this particular adenovirus used in the current vaccine trial is not the one found in humans, but in another species, and that it doesn’t cause disease naturally in humans. More than this, this adenovirus has been genetically engineered so that it’s unable to replicate in humans.

“So even though it is a vector, it’s been genetically engineered such that it is unable to replicate itself and to form more adenoviruses once injected into the body,” he said. 

Those with comorbidities have been included in the study. Is this trial safe for them?

People over the age of 65 years, as well as those with underlying medical conditions such as diabetes, heart disease, or hypertension, are at greater risk of developing severe or critical Covid-19 illness, if infected with the SARS-CoV-2 virus.

Madhi said that under normal circumstances, the initial evaluation of such trials is limited to healthy individuals who don’t have comorbidities that might compromise their immune system, but that, in this particular trial, the team of scientists have departed from the norm because of the urgency of the situation. However, he also explained:

“In the age group of 18-65 years, we are including individuals that might have hypertension or diabetes, provided they’re well-controlled. So if someone is unstable on treatment, then they wouldn’t be eligible for inclusion. Or if they’ve suffered severe consequences from hypertension, such as kidney failure, then they also wouldn’t be included in the study.”

Although they're including some volunteers with comorbidities, their team also has a threshold at which they need to limit participation of these individuals for two reasons, said Madhi.

Firstly, he explained, they need to show that a vaccine is safe in a relatively healthy population, and secondly, they need to verify how well this vaccine works under optimal conditions before they can experiment with it in other individuals that might be immunocompromised.

“It might well be that we show that the vaccine works in healthy individuals but not in people that are immunocompromised like people with diabetes, hypertension or HIV, as an example, or people over the age of 65. Their response to the vaccine might be inferior to that of other people. But that doesn’t mean that immunisation won’t necessarily protect them.”

Madhi explained that in the case of vaccines, there’s a threshold in terms of the immunity of the population that must be reached. Once it is reached, the particular virus then becomes less efficient when transmitted, as those who have been vaccinated will have developed immunity to the virus, and in those people that are not vaccinated, they will indirectly become protected as well.

“This disrupts the chain of transmission of those organisms,” said Madhi, referring to the process of herd immunity.

READ | 6 things you need to know about the first SA Covid-19 vaccine trial

READ | Why vaccines need to be tried and tested in different populations across the world

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