Dr Gonasagrie (Lulu) Nair, Clinical Research Site (CRS) Leader and Senior Medical Officer for the Desmond Tutu HIV Centres Emavundleni research site, and Dr Katherine Gill, CRS Leader and Senior Medical Officer for the Masiphumelele CRS
I think getting a vaccine out quickly will be a game-changer for South Africa, especially a one-shot that doesn’t need a rigorous culture.
Moderator: Tian Johnson
Complied by Vivienne Naidoo
Queries: info@africanalliance.org.za
Webinar Recordings & Supplementary Materials:
https://www.jnj.com/coronavirus/about-phase-3-study-of-our-covid-19-vaccine-candidate
https://www.ensemblestudy.com/#!/
https://www.samrc.ac.za/research/ethics/guideline-documents
WHO
Dr Gonasagrie (Lulu) Nair, MBChB, DCH, DT&H, PGDip Health Research Ethics, MPH Dr Gonasagrie (Lulu) Nair, is an experienced public health specialist and clinical trialist. As a younger public health sector clinician in KwaZulu Natal, the epicentre of the South African epidemic, Dr Nair understood the devastating impact of the HIV and TB epidemic. She subsequently shifted her focus to public health. She has over 18 years of research experience ranging from protocol development to implementation and is experienced in conducting all phases of clinical trials. These include HIV prevention and treatment trials, vaccine, microbicide, PrEP, HPV and Tuberculosis studies. She has served on two South African institutional biomedical ethics committees and has been the two HIV prevention studies protocol chair. Dr Nair is based at the Desmond Tutu Health Foundation’s HIV Centres Emavundleni research site in Crossroads. She is hands-on, directly overseeing all study procedures and management issues at the Clinical Research Site (CRS) from protocol development to community engagement.
Dr Katherine Gill MBChB, Dip Pall Med, Dip HIV Man is an experienced HIV clinician and research physician. Dr Gill serves as both Clinical Research Site (CRS) Leader and Senior Medical Officer for the Masiphumelele CRS, a research Site of the University of Cape Town Clinical Trials Unit (UCTCTU). She has an interest in HIV prevention and adolescent health services. She is currently working on several vaccine studies for HIV, COVID-19, and Human papillomavirus (HPV). She is currently completing a masters in public health at the University of Cape Town.
QUESTION AND ANSWERS
*This section contains a transcribed account of the Question-and-Answer Session*
What have you learned in this particular community engagement process for this trail – (ENSEMBLE) trial?
So I think for us, the big challenge was that we couldn’t employ our tried and tested methods of engaging with the community and recruiting participants. We worked under lockdown conditions, rather than engaging through face-to-face meetings and going out into the community. We had to look at electronic platforms, like WhatsApp, instead of meeting stakeholders, sitting down, discussing the study, meeting with participants, doing door-to-door recruitment, meeting in schools and other community locations. That was a challenge because we had to reach out to groups who usually don’t use social platforms. That was a little bit of a challenge reaching out to older participants. The community teams were engaged. They sat down with people, got them onto social platforms like WhatsApp and taught them how to use emails. That kind of thing was critical after recruitment and being enrolled in the study. That’s from the Emavundleni perspective. And over to you, Katherine.
I think very similarly to us at Masiphumelele site. One of two very different things about this study was the rapid timeframes to recruit all of your participants. For us, we only started at the end of November. So we had about two or three weeks to recruit all of our participants. So that for us is very different. And I think the engagement piece is sacrificed when you move fast. So as Lulu said, we did have to be creative. The other thing that was quite new for us was recruiting a different kind of person. We were going specifically for older people, and often quite challenging to engage them on social media. So we had to think carefully. What made the study easier is that people in our area tend to believe in vaccines. And the vaccine is quite an easy thing to present to somebody because people know that children are vaccinated against diseases. So for us, it was it wasn’t difficult at all to recruit people. People were very keen, and I think people’s general literacy, around COVID, is relatively high. People have had a year to absorb what COVID means. And I think with the lockdowns, people also understand the severity of this disease. We didn’t have any issues, recruiting them. We had long lines of people waiting to come and join. The other thing that people have appreciated is that it might be a long time before a vaccine is widely available. And this was a way to get access to a vaccine earlier.
How were these clinical trial sites chosen globally, particularly in South Africa?
So I think it was based on the experience of the clinical trial sites. We were also recruited through a network that we work with, the HIV Vaccine Trials Network, having had experience with implementing HIV and TB trials in the past. And so I think it was looking at what infrastructure the sites had in place, the history and success with recruiting in previous trials. And how quickly we could do that. We would have sufficient space to implement the study; we would have the catchment population to work with. I think all of that was considered. And we had to provide reassurance that we could do this very quickly.
In October, we hadn’t understood or to a large extent, even heard of a COVID variant. Now that we do, what do the ENSEMBLE interim results mean for the variant discussion?
Okay, so I think with the variants, there is a very specific variant in South Africa(501Y.V2). What’s nice about the study is that we know now specifically how well the Johnson & Johnson J&J vaccine works against that variant. And it’s the same with the Novavax study; we now have actual data on how it works. And I think the thinking is that the virus will continue to mutate it. There are already three named variants. So I think that it will carry on mutating. And I think the drug companies will have to tweak the vaccine as they do with the flu vaccine, every year, I don’t know every six months, every year to make sure that it’s active against whatever variant is prevalent at the time. And I have heard data from Moderna that they don’t think that this will be too difficult. But it will require some ongoing surveillance to see which variants are prevalent in which areas and then getting a vaccine that can work against those variants. The other thing to remember is that despite the different variants in the different countries, the J&J vaccine could prevent death and severe illness across all the variants. And that’s something that is a definite take-home message. So while it didn’t work against the mild version of our variants, it worked well to prevent death and severe illness. And the scientists are unpacking that because it is an interesting idea that it didn’t prevent mild disease, but it could prevent severe illness and death. But I think that’s the critical take-home, that it can prevent death and severe illness across all the variants seen in the study.
Lynette Mabote is asking about severe adverse events. Did you see any? Could you give a summary or a snapshot of what those were, if there were any? And how are those managed?
So I think Lulu presented in her presentation. There weren’t any severe adverse events seen. For my site, we definitely didn’t have any. What we did see was that not many of our participants had any reaction to the vaccine. So what we always do on vaccine studies is after you’ve given the vaccine, you observe your participant for half an hour after the vaccine to ensure that they’re okay. We didn’t see any adverse effects afterwards. It seems to be very well tolerated. I’m not sure about Lulu.
I have to agree with Katherine. We didn’t see any adverse events at all. We usually see a localized reaction to the injection, redness, swelling, and so on, we saw nothing of that sort. And it was quite surprising. We questioned whether people were even pointing accurately because we were so surprised that we did not see any of these. We have a mechanism in place to follow up with participants and ensure that they are reporting in a timely fashion.
Do we know how long immunity would last in someone with symptomatic infection versus those who have had the severe disease? And do these results mean anything for that immunity discussion?
I think we don’t know that answer about how long immunity to natural infection lasts. Katherine and I are currently involved in a study where we’ve enrolled participants or patients who have been infected. And we are following them up for a period of over a year to determine how long immunity lasts. So we’re seeing them periodically, collecting swabs and blood to try to ascertain how long immunity via natural infection is conferred.
What is interesting about the J&J study is that they did enrol people who had previously contracted COVID. We didn’t necessarily ask people, but it wasn’t an exclusion like some other studies. And that is a secondary objective. They will look at that after a year or after two years to see who had antibodies at baseline and whether they are reinfected. So that’s a much longer analysis. I don’t think you will get that in the first month. So I think the data on that is coming in, and it will be really interesting. And I’m glad we didn’t exclude people who’ve had COVID, especially not after the second wave. A lot of us have now had COVID and are wondering whether we should get vaccinated.
What are your thoughts on eventual access? When will this vaccine end up in the bodies of those who want it and those who need it? What are your thoughts on the delays in getting vaccines, irrespective of which vaccine it is, to communities who need it?
The answer to this is that it’s just as frustrating for researchers. We are also feeling angry and frustrated that our sites have participated in these studies and don’t have access. So we’re very much on the same page. These vaccine studies mean that it gives us many more options, which is why I was praying that this vaccine would work. We don’t have to rely on one drug company, who would have a monopoly and could charge as much money as they wanted to. And so I think, if a lot of these vaccines work, it will make access faster. So I think that’s a good thing. If we’ve got ten, and all ten are working, we will get access quicker. Because we are making the vaccine in this country, we’ll be more likely to access the J&J vaccine.
I also think that these results are good news, as Lulu said, the vaccine can prevent severe illness and prevent death. And that for South Africa is going to be a game-changer. It’s going to keep people out of hospitals. Hospitals already have 100% bed occupancy. And I think getting a vaccine out quickly will be a game-changer for South Africa, especially a one-shot that doesn’t need a rigorous culture. So I think for me that the J&J results are great. Access is always difficult, and I think it’s going to need a lot of activism to keep the government on track. Probably similar to what we saw in the early days of HIV and antiretroviral access.
I think it’s wonderful that the study participants will get the vaccine first, that those who were on placebo will have access as soon as the protocol can be amended. Providing the vaccine through one central mechanism is an excellent idea because it will ensure equitable access, no matter who you are, you will stand in the queue for the vaccine, and it will be rolled out according to your risk. And I think that’s a good thing.
If we could have one lesson learned and one reflection from both of you, specifically, around ENSEMBLE? What is your takeaway message?
Yes, I think my take-home, as a researcher, I naively thought that we would automatically get it if we participated in the J&J vaccine. If I look back on that thinking, now, it is naive. And I think going into that you asked what would be different if we did a new vaccine, I think going into a new vaccine study with more terms and conditions. We have an excellent infrastructure in this country to conduct clinical trials. And I think we need to be better at negotiating access upfront. So I think that would be my learning point, that you can’t assume that access will happen, especially when you’re working with pharma.
When we think about implementing our trials and compile our informed consent documents and make our ethics submissions, we always include a statement about post-trial access. And we think about post-trial access, and we discuss this with our communities when we do community engagement before the trial starts. And we need to do more than just having that one line saying, you know, there will be post-trial access, and placebo recipients will receive the active product. We need to think more and maybe have a stronger statement regarding benefit sharing in our informed consent documents and when we engage with our communities.