In the race to get as many people as possible vaccinated, the government should leverage the considerable reach of the country’s pharmacists and GPs to amplify the public health facility response, the two lead investigators in South Africa’s vaccination trials said this week.
Professors Shabir Madhi and Glenda Gray discussed issues around the country’s vaccination programme during a webinar with Maverick Citizen editor Mark Heywood, sponsored by the Konrad Adenauer Stiftung on Thursday night.
Responding to concerns raised about the efficacy of the available vaccines against a new, more infectious strain of the virus in South Africa, Madhi said in the coming days the information they are going to provide will be “the most important information globally on whether vaccines will work against the new variant”, stressing that their results will have global implications for the roll-out of Covid-19 vaccines and their development.
Gray is the lead investigator in the South African trial for the Johnson & Johnson vaccine. She is a vaccine scientist and the president of the Medical Research Council.
Madhi was responsible for introducing the latest vaccine for pneumococcal disease to South Africa in 2009. Apart from being the dean of Health Sciences at Wits University, Mahdi is also the principal investigator in the Oxford-AstraZeneca trial.
Due to the urgency of the pandemic, Madhi said there was no time to wait for long-term safety data.
“We cannot be in a situation where we wait five years to get long-term safety data, by which time the pandemic would have passed and the number of lives that would’ve been lost would be in the hundreds of thousands – let alone in the millions,” he said.
The two vaccines using novel technology, he explained, teach the body to attack the spike protein on the virus. This is an important part of the coronavirus, as this is how the virus attaches to human cells. He said the two vaccines either introduce the spike protein RNA to the human body, or through a carrier virus that is not harmful to humans or has been deactivated. Once that is injected, that RNA is released into the cells.
“The RNA is then read and sort-of provides the blueprint for the cells to start producing protein,” he explained.
“Importantly, this RNA does not integrate into the [recipient’s] DNA. It does not enter into the nucleus of the cell, which is where the DNA is. It is impossible for this RNA to alter the [recipient’s] DNA. I think it is pretty important to emphasise,” he said. “Because this is not a live virus it does not have other enzymes that would allow for such an integration.”
The vaccine then teaches the body to make proteins that only attach to the coronavirus, not to the cells.
The Pfizer and the Moderna vaccines injected messenger RNA (mRNA) directly while the Johnson & Johnson and the Oxford-AstraZeneca vaccines use carrier viruses or vectors to deliver the RNA to the cells.
Researchers have been working on mRNA vaccines for the past decade to develop a vaccine against cancer.
“The more tried-and-tested approach is where we take the [spike] protein and inject that into the individual. The vaccine that is the furthest down the line and one of the two studies we are leading in our unit is the Novavax vaccine,” Madhi said.
This technology is also used in vaccines against whooping cough (pertussis) and diphtheria.
“The last one is the virus-based vaccine. These are vaccines that actually use the SARS-CoV-2 virus itself and then either attenuating [genetically modifying] it or inactivating it,” Madhi said, adding that the science around attenuating the virus was still new.
The Sinopharm vaccine, developed by a Chinese company, uses an inactivated virus. This technology is also used in the polio vaccine.
There are more than 40 vaccines in the human trial phase – five of which have been authorised for human use by different regulatory authorities.
Gray said to establish whether a vaccine is safe, they determine whether there was a good immune response and if it will prevent infection. She said they also look at a scenario where a person, who had been vaccinated, gets infected to see if the vaccine will shorten the duration and the severity of the disease. The third question, which is critical, she said, is whether or not the vaccine reduces transmission in the community.
“We give vaccines because we want to control the epidemic. It is the only way to control the epidemic. We use vaccines for public health benefit to try and prevent communities from being infected. That is why we try to obtain herd immunity by using vaccinations,” she said.
A vaccination programme will ease the disease’s burden on the public health system, have an economic benefit and keep schools and universities open.
For a company to register a vaccine, it must present evidence to the South African Health Products Regulatory Authority. “We have seen from the trials that these vaccines have worked irrespective of age, sex and ethnicity.”
The vaccines also work for people with a number of chronic conditions including hypertension, diabetes, lung disease, and cancer.
“They work quite spectacularly. Moderna and Pfizer [vaccines] … are 90-95% effective. What we have seen is [that] vaccinations will save people’s lives,” she said.
“We do need to assess the impact of the disease on ongoing transmission,” she explained, saying that they already know that the vaccine reduces viral load in asymptomatic individuals and makes people less infectious.”
She stressed that there was an urgent need to save lives, which a vaccine would be instrumental in achieving.
On the issue of vaccine safety for use by children and pregnant women, both Gray and Madhi said adult trials were first being conducted (excluding pregnant women) in order to establish safety, then children and pregnant women would follow.
Gray said some countries were already testing and tracking the impact of the vaccines on children.
The World Health Organisation believes it is in the best interests of pregnant women to get vaccinated, particularly because the virus increased the risk of premature birth.
Common side-effects of the vaccination are tenderness in the needle prick area, mild fever and flu-like symptoms, but these should only last for a few days. “We have a good handle on short-term safety,” she said.
Grey stressed that even where less effective vaccines were used, herd immunity could still be achieved. “The more coverage you get, the more public health benefits you will get.”
Madhi told Heywood that from a public health perspective it would be counterproductive to exclude people like undocumented migrants from receiving the vaccine.
“To bring about interruption of viral transmission you cannot exclude anybody. Covid-19 will be with us for decades to come. We must try to avoid a resurgence. Our vaccination programmes must be inclusive.
Discussing the difference between vaccine-induced immunity and natural immunity, Madhi said so far, natural immunity seemed to last up to nine months. In cases of infection by other coronaviruses like SARS and MERS, scientists found natural immunity can last up to three years.
Madhi said he would estimate that vaccine-induced immunity would last as long as naturally acquired immunity.
An important difference, he noted, is that “vaccines will result in a much more predictable immune response. As the vaccination induces the development of memory cells in the body that know how to neutralise the virus. This ensures that there is a much quicker response when a person is exposed to the virus again.
Those who survived Covid-19 or tested positive should be vaccinated as well, as per the WHO’s recommendation.
Grey said it was important to track people on vaccine trials because this is where the information regarding the time needed for re-vaccination will be sourced. Scientists currently only know the short-term efficacy and still need to track the long-term durability in order to determine a good time for a booster shot.
Asked what vaccine South Africa is likely to get, Grey said that the country was lucky to see that the AstraZeneca vaccine as well as the Moderna and Pfizer vaccines have all shown great efficacy.
“All three of those vaccine choices for South Africa would be great. We would like to see all of them coming to South Africa. I would like to see if the Johnson & Johnson study works… I would like to see that vaccine introduced [in South Africa] as it is an emergency vaccine. It is a single dose vaccine and its indication is for emergency use… to protect the healthcare worker or the individual. It may need a booster at a later stage. For South Africa I think we would like to see as many vaccines come in and evaluate the roll out that we understand the long-term safety.”
Madhi said the Pfizer vaccine, which has to be stored at extreme temperatures of around -80ºC, was not fit for large-scale rollout but could, for example be used in the healthcare field.
Gray said it is worth remembering that there is constant innovation in the vaccination field and it is likely that the Pfizer developers will solve the problem of low temperature storage in their second generation vaccine.
On vaccine safety, Gray said the vectors or carrier viruses used in some of the vaccines have been used in other vaccines for Zika, Ebola and malaria.
“Hundreds of thousands of people have received these vaccines. We know the vector is safe. We study the safety of the RNA being introduced. We must still establish long-term safety,” she said.
If the regulators are happy with the short-term efficacy, the vaccine will receive a short-term registration with an additional requirement that the data from the roll-out is shared to establish long-term safety.
Gray and Madhi agreed that South Africa needed to get immunisation campaigns going and stressed that public-private partnerships would be vital to the success of the vaccine rollout.
On the use of Ivermectin, Madhi said studies that are available can by “no stretch of the imagination” be interpreted that it can be used as a prophylactic to avoid infection by the coronavirus. And in the absence of robust scientific evidence, those who decide to use it “will be taking a chance”. DM/MC
Watch the full webinar here.