Inside story on Novavax, SA’s next Covid-19 vaccine hope – Prof Shabir Madhi, Alec Hogg

In the global race to find a reliable Covid-19 vaccine, two studies have been conducted in South Africa. Oxford University's drug and now the Novavax vaccine, which will call on 2,900 volunteers to assist in trials. University of the Witwatersrand professor Shabir Madhi, whose unit was selected by US drug company Novavax to run a critical 2b trial of its coronavirus vaccine, says that the trials will generate evidence of how the vaccine would work in the African context. The third study, headed by Professor Glenda Gray, will likely start towards the end of September. – Claire Badenhorst.___STEADY_PAYWALL___.Well, it's a warm welcome to Professor Shabir Madhi who's well known in South Africa as the head of the Infectious Diseases Research Unit at Wits University. You've been busy over the last few months, as I guess many people in your profession have. But a big announcement today, that there's another vaccine trial that's going to begin in South Africa through Novavax. Can you just explain a little bit about your relationship with Novavax and how that helped to bring the trial here to South Africa?.I was the national principal investigator and one of the key investigators in a previous vaccine study of theirs, which was a vaccine that was targeted at vaccinating pregnant women to protect their young infants. It's a vaccine against RSV (Respiratory syncytial virus) and South Africa was one of many countries that participated in that study, and the data that came out from South Africa, in fact, was of extremely high quality. And what we were able to show in that particular study is our ability to do high quality research. In fact, the results that came out from South Africa were highly promising in terms of that particular vaccine. So, that is really the background in terms of where I have developed a relationship with this particular company. The RSV vaccine study is similar to the study that we are about to embark on with Covid-19, with Novavax, was also funded by the Bill and Melinda Gates Foundation..Did you have to twist any arms to bring them to South Africa?.Ja, without question. So, I think what we need to appreciate is that right now, globally, there's huge amount of competition between scientists to be taking part in these sort of vaccine studies. So, it's not that Novavax were rushing and banging on our door for the study to be done in South Africa, but with the relationship that I had developed with them, it provided me an opportunity to reach out to them to see if they would be keen for a study to be conducted in South Africa. This time round it took longer than it took the University of Oxford to convince them that South Africa is a place for these vaccine studies to be done. But ultimately, fortunately for us, we've been successful in bringing the study to South Africa..Now, you're also driving the Oxford University vaccine of which there's much interest in South Africa, not least because we've got a lot of people who've invested in it through the Oxford company. But that's seven weeks in. For the outsiders, does this mean that Oxford is seven weeks ahead of the Novavax vaccine?.Well, certainly in South Africa they are and probably at a global level as well. So, Oxford are pretty much in Phase 3 studies already. In South Africa, we're doing the equivalent of a Phase 2B study which still allows us to get an answer as to whether the vaccine protects against Covid-19. But they are doing much larger studies in the United Kingdom as well as Brazil, and they are planning on starting a much larger study in the United States, and those are sort of the final pivotal studies, the Phase 3 studies..So, Novavax at this point are at Phase 2, which is one step behind where Oxford is. So, certainly the University of Oxford's vaccine candidate, the one that's now been taken on by AstraZeneca is ahead in terms of clinical evaluation. But which of the two vaccines, if either, actually eventually ends up protecting against Covid-19? That is the question that we're trying to address right now..Read also: How far are we from a trustworthy Covid-19 vaccine in SA?.What's the difference between them?.So, they're fundamentally different in terms of their construct. The Oxford vaccine is what we know as a non-replicating vector-based vaccine, where it uses, sort of, an adenovirus. It gets that adenovirus to be able to express the spike protein, which is a protein that's important to the virus, to the SARS coronavirus, and that's delivered into the human body. So, it's a much different technology and there's very few vaccines that have been licenced using that sort of technology. In fact, right now there's only a single vaccine, which is the Ebola vaccine that's been licenced using this vector-based technology..The Novavax technology is what we call a protein-based vaccine, which is more sort of a traditional approach in terms of vaccine development. But they've been able to sort of fine tune it in terms of the manner in which it's actually delivered through the immune system, coupled with an adjuvant, which actually enhances the immune response. So, it's a much more traditional tried-and-tested method in terms of vaccine development compared to vector-based vaccines. That is really where they differ..They do show differences also in terms of the preclinical studies, including in non-human primates, but it's difficult to make comparisons at the same time because the design of the studies are slightly different. But what we saw with the Novavax vaccine candidate, and importantly, from a public health perspective, is that in the animal models, is able to protect both against upper airway infection as well as lower airway infection. And a vaccine that's able to protect against upper airway infection would be extremely useful because that's the type of vaccine that you require to accelerate what we call herd immunity, where a certain percentage of the population is only vaccinated, yet the benefits basically extend to a much greater percentage or almost all of the population..You mentioned that the Bill and Melinda Gates Foundation are helping to support the Novavax vaccine. I think in your statement, it said $13m that they are contributing. Has there been similar help for the Oxford vaccination study?.Correct. So, both of the studies that are being conducted in South Africa are actually being funded by the Bill and Melinda Gates Foundation. Both AstraZeneca and Novavax, as you might know, both of them are forming part of Operation Warp Speed in the United States, where the US government has put up billions of dollars to sort of procure vaccines that are not yet really licensed. But in terms of the clinical development of the vaccine and the evaluation of vaccines in low and middle income countries, particularly in South Africa, that programme is largely being funded by the Bill and Melinda Gates Foundation. Again, the reason for that, like I mentioned earlier, is that there simply isn't any shortage of countries and sites for these vaccine studies to be conducted..At the end of the day, for these vaccines to be licenced in Europe, for the vaccines to be licenced in the United States, unfortunately, the requirements on part of the regulated authorities in those sort of regions is that much of the evaluation in terms of the pivotal Phase 3 studies needs to be undertaken in those countries, or countries of a similar sort of demographic profile..So, as far as South Africa is concerned, why is it important that the vaccine trials happen here?.So, the legacy of vaccines, many life-saving vaccines is that there has been anything between five to 20 year leg, between the time when a vaccine becomes licenced and available in high income countries, compared to when it's rolled out in low/ middle income countries. Often the reason for that is because of the absence of data to actually quantify how well those vaccines would actually work in low/middle income countries..So, those sort of clinical studies end up only being done after the vaccine is licenced in a high income country, in many African countries. So, the WHO often does not have the evidence to make a firm recommendation that this vaccine would be useful in low/middle income countries and it would work as well as it works in other settings. So, for us to be able to understand just how well these vaccines work, and in fact, which of the vaccines would probably be more suitable for the African context, it's essential that we get into the game of evaluating these vaccines at an early stage of its development, so we can shorten that period of time between when the vaccine is eventually available and when the recommendations come out from the WHO and others, for it to be included in immunisation programmes on the African continent.."With the Novavax study, what we've been able to negotiate is that should the vaccine be shown to be effective in South Africa, we would pretty much go to the front of the queue in terms of possibly being able to access a vaccine." .The Bill and Melinda Gates Foundation has actually provided a grant to the Serum Institute in India for the Serum Institute to start producing both of these vaccines at risk. So, again, without knowing whether these vaccines are going to work, the Bill and Melinda Gates Foundation is making that investment. So, South Africa would be highly competitive in terms of being able to access these vaccines at an early stage because of us having been involved in the clinical development of these vaccines..That's really good news that they would be prepared to support the production of the vaccine at risk without it even being stamped or approved yet. But presumably they wouldn't have done that just to throw money away. There must be a pretty good chance or a pretty good feeling that it is going to work..Ja, without question. It is a calculated gamble, obviously. And basically what you're seeing is that, from the non-human primate studies, as well as from the initial Phase 1 studies for both of these vaccines, they clearly sort of check the boxes in terms of vaccines that are very likely to be able to protect against Covid-19..So, unlike, as an example, the Russian vaccine, which underwent almost no clinical studies, in fact, they studied fewer than 100 participants before they licenced the vaccine. Going into production with those vaccines, you're really taking a huge gamble, whereas with these vaccines that we're referring to, it's a much more calculated risk that you're taking on because you've got some data to show that these vaccines are very likely to protect..The question is, what level of protection are we going to get, and whether it's going to protect against both severe disease as well as against upper airway infection, to try to reduce the transmission that might occur..Read also: Could Oxford's Covid-19 vaccine, on trial in SA, really be the one?.From the mass media perspective, we have seen a lot of discussion about the race for a vaccine. What happens if, and you lean on both of these, personally, what happens if they both work? Which one would then be applied?.Well, the bottom line is for Covid-19 vaccines to make a difference in terms of this pandemic, we need more than one vaccine to work.."We actually need at least five vaccines as a minimum to be shown to be effective.".And that's the only way in which we'll be able to scale up production in terms of the quantities that are required to be able to immunise even 50% of the global population. If we just have a single vaccine that works, unfortunately, South Africa, as an example, is unlikely to get those vaccines at any meaningful quantity until after a pandemic has passed the spike. So, it's absolutely essential that we have multiple vaccines that actually are shown to work, not just two vaccines, but at least another two to three vaccines..The chances of that, unfortunately, is fairly slim because, again, the history and legacy of vaccines is that it's only about 10% of vaccines that go into clinical trials in humans that they eventually licence, that eventually are shown to be safe and effective. So, even with the six, seven vaccines that are already in Phase 3 studies, even if two of those seven vaccines eventually are found to be efficacious, that itself would be a huge, huge success in the scientific community..I don't think it's about which of these two vaccines, it's just the ambition to at least have a handful of vaccines that are shown to work over the next few months, to enable at least about 10 to 20% of the global community being vaccinated over the course of the next 12 months..Sounds a little like oil exploration. You can drill in holes and if you're lucky, you'll get one that works. How many other vaccine trials are being conducted in South Africa right now?.So, right now these are the only two studies that have been conducted. There's a third study that is likely to start towards the end of September. That study is being funded by the NIH and it's part of a multi-country, multi-centred study. It's a vaccine that's produced by Johnson and Johnson and it's what we call an adeno 26 virus vector vaccine..So, similar to the chimp adenovirus vector vaccine, but it's using a different adenovirus construct. So, like I said, that study will be undertaken by Professor Glenda Gray in South Africa through the HIV Trial Network. But South Africa will be one of many countries that will be contributing to the participants in that particular study..Just as a broader question to end off with, for Wits University to be selected for both of these vaccine trials is surely a recognition of world class, or that the university is, despite the critics, very much recognised as a world class institution..Ja, certainly so, and especially when it comes to vaccine development. My research unit has been doing Phase 1 to Phase 3 studies on new vaccines for the past 25 years. And in fact, we've had a number of firsts on the African continent and from any low income country in terms of showing which vaccines are of public health value for children, as well as for adults, and pregnant women. So, this is probably one of seven vaccines where we've been pretty much in the lead in terms of its clinical development. And like you mentioned, it's not just about my research..I think, unfortunately, the potential of Wits University in the field of knowledge is something that isn't truly appreciated. Unfortunately, the blame lies on the part of the university itself in that it hasn't really harnessed that expertise to the same extent that it has been harnessed and consolidated at the University of Cape Town. But certainly, and I don't think it's just about being leaders on the continent. In terms of the type of work that we do, we are highly competitive on the international stage, and that's the reason why we can convince companies for us to form part of their development profile..Covid-19 vaccine candidate from Novavax starts midstage trial – Wall Street Journal.By Jonathan D. Rockoff.Novavax Inc. said Monday its experimental Covid-19 vaccine is starting the second phase of testing to see if it can safely protect against the new coronavirus..The vaccine candidate is the latest to move a crucial step closer to wide use, behind a handful of shots that have already started the final stage of testing and one developed in Russia that the government there cleared after limited study..Novavax said its vaccine could begin the large final stage of testing by September..The company's so-called Phase 2b trial will take place in South Africa, which is among the countries hit hardest by coronavirus, with more than 587,000 cases and over 11,800 deaths, according to data from Johns Hopkins University.."Because South Africa is experiencing a winter surge of Covid-19 disease, this important Phase 2b clinical trial has the potential to provide an early indication of efficacy, along with additional" data about the candidate's safety and the immune response it generates, said Dr. Gregory Glenn, Novavax's president of research and development..The study will also evaluate the vaccine in a set of HIV-positive adults whose disease is well-controlled by medication, the company said..Vaccines from Moderna Inc., a collaboration between AstraZeneca PLC and Oxford University researchers, and a partnership between Pfizer Inc. and BioNTech SE recently began the large, final-stage trials..So has a vaccine under development by the state-owned China National Pharmaceutical Group, or Sinopharm, according to the World Health Organization. Saudi Arabia said this month it will begin a Phase 3 trial of an experimental Covid-19 shot from China's CanSino Biologics Inc..Health officials in Russia and the West have raised concerns about the vaccine that the country's government recently approved for use, before a third round of testing starts..The Bill & Melinda Gates Foundation is giving $15 million to help support Novavax's Phase 2 study, which the company said could help support the vaccine's green light for use in South Africa. The nonprofit Coalition for Epidemic Preparedness Innovations is funding the manufacturing of doses used in the trial, the company said.."The major motivation for the Covid-19 vaccines being evaluated at an early stage in South Africa is to generate evidence in the African context on how well these vaccines work in settings such as our own," said Dr. Shabir Madhi, a vaccinology professor at University of the Witwatersrand, who will lead the study..Novavax's vaccine consists of two shots given 21 days apart. The shots deliver a protein resembling the spike jutting out from the new coronavirus to trigger the production of antibodies and immune cells that fight off the virus. The shots also contain a component, called an adjuvant, to boost the immune response..The Gaithersburg, Md., company said it plans to provide the data collected from the South Africa trial to the U.S. Food and Drug Administration as part of the evidence on its vaccine candidate..The company also said it plans to start a second midstage trial in the near future in Australia and the U.S..There are three stages of drug or vaccine testing, starting with a first phase that researchers use to make sure the shot is safe and look for clues that it works..Novavax said this month its vaccine candidate was generally well-tolerated in its Phase 1 study and produced promising but preliminary immune responses in subjects, namely the neutralizing antibodies that could fight off the virus..In the Phase 2 study in South Africa, researchers aim to examine the shot in 2,665 healthy adults, along with another 240 adults who have tested positive for HIV and are well-controlled on medication and have a low viral load, Novavax said..Other companies, including Pfizer, have also said they plan to study their experimental vaccines in people who are HIV positive..People who are taking an effective HIV treatment appear to have the same risk of getting Covid-19 as people who don't have HIV, according to the U.S. Centers for Disease Control and Prevention..The U.S. government has agreed to pay Novavax $1.6 billion to fund late-stage development of the company's coronavirus vaccine, establish large-scale manufacturing and for 100 million doses..Write to Jonathan D. Rockoff at Jonathan.Rockoff@wsj.com

Inside story on Novavax, SA’s next Covid-19 vaccine hope – Prof Shabir Madhi, Alec Hogg

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