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BlueSci Podcast

Released 1st June, 2020


BlueSci 0:05

Welcome to the BlueSci podcast, brought to you by Cambridge University Science Magazine. Every two weeks we speak to local researchers, university staff and students and anyone who works in science to learn about their research and activities, hear about the work that they do, and uncover what goes on behind the scenes. If you want to get in touch with a question, suggestion or just want to be featured on the podcast, just drop us a tweet. Our handle is @bluescipod and you can also email us at bluescipodcast@gmail.com.

Ruby 0:46

Hello, everyone. This week we spoke to Dr. Chinedu Ugwu, who is a lecturer and research fellow at the Africa Centre of Excellence for genomics of infectious disease in Nigeria. He has just won Cambridge Africa Alvarado COVID-19 emergency Research Fund to study the immune correlates of protection to SARS Cov 2 in Nigeria. We speak to him about his upcoming project and how he has repurposed a research framework successfully in combating Lassa fever and applied it to the current COVID-19 pandemic. We hope you really enjoy this episode. And don't forget to share it with anyone that you think might be interested in learning more about the SARS-Cov-2 virus.

Simone 1:33

The Blues a podcast is sponsored by Greiner bio one, who supply laboratory diagnostic and medical products to research institutions, higher education, the NHS and others across the UK. For details of the full product range, visit www.gbo.com.

Ruby 1:54

Welcome Chinedu, thank you so much for joining us. Can you tell us a little bit about yourself and your background and the project that your new grant is funding?

Chinedu 2:05

Okay, my name is Chinedu Ugwu. I'm from Nigeria. I'm from the south eastern part of Nigeria. And about my backgroud...my undergraduate was in veterinary medicine at the University of Ibadan. Then I did a master's in Oxford. I came to Cambridge for my PhD. I work in Nigeria, I work in a university called Redeemers University. And where I do my research is in a centre called the African Centre of Excellence for genomics of infectious diseases. So basically, we focus on looking at genomics of infectious diseases, so I joined them in 2018. So we mostly deal with different infectious diseases like viral hemorrhagic fever, Ebola, lassa fever. I'm pretty proud to say that the centre did the sequencing for the first case of the Coronavirus in Nigeria. So for the COVID work in the centre, we are mostly involved now in testing and diagnosis. So we get samples from every hospitals and then we diagnose using PCR and then we also go ahead and sequence some of the samples to see the genome and spread of the outbreak. When I came back to Nigeria, I came back on the project funded by the BBSRC, to study Lassa fever in Nigeria, and also to understand the immune correlates of protection to Lassa fever. So what are the features of protection when you get Lassa fever. The project is two years now, and we've gotten to good results, and hopefully we'll finish them soon. So when the COVID outbreak happened, I suppose since it's a novel virus, and there's not much known and the world is racing to produce a vaccine. I thought, as we're already doing in correlates of protection for Lassa fever, so we could do the same for for COVID such that when the vaccine is available, we'll understand, okay, what are the features of protection, so you will be in a better position to assess the efficacy of the vaccine. So I approached Cambridge-Africa and told them that I have this idea. They said, okay, they have the emergency funding that I can send my proposal and they will see. So I then wrote up the proposal and then sent it for review, and we submitted and we're lucky to get funded. So the aim of the SIP-NG project is basically one to study the main criteria for protection to SARS-Cov-2 in Nigeria. So if you were infected by SARS-Cov-2, and then you are treated and you say, right, what are the features of your immune response? So hopefully those are the things that made you survive. So what we intend to look out with the project is to look at your, the antibody response. And then we'll also look at your T cell response, which are the two arms of the immune system. So it was easy to design this project, because we already have a template from the last project we already been,right?

So we measure the antibody response from survival, we also measure the T cell response. The other thing we do is we also measure different cytokine responses. So we have an overview of the features of infection. And then we can then advise when the vaccine trial is running, but we can be better prepared and better informed.

Simone 5:40

So that sounds really interesting. And I was going to ask for someone that's not doesn't have a biology background, but basically the information that you'll get from these studies, once the vaccine is out, how can this information kind of help us use the vaccine better in the future?

Chinedu 5:52

Okay, so if I give you a vaccine, I'm expecting you to have a good antibody response and I'm expecting you to have a good T-cell response. If the vaccine cannot induce that kind of response, then it means that the efficacy of the vaccine is not very good, right? So they have to go back to the drawing board. So it's good to have some information before you do clinical trials, because it helps you to assess the clinical trial. So it helps you to know, whatever you are giving is giving you results.

Ruby 6:18

I guess as well, it's important to know kind of what you might want to be looking for once you've administered a vaccine, if it is similar to somebody who's already had the virus.

Simone 6:29

And in terms of the way you were seeing how you were doing this work, the kind of protocols that you set up and now adapted for COVID you were actually using for something else before, do you think having those protocols in place and having to kind of do those kinds of studies and other infectious diseases has been useful for a situation like this?

Chinedu 6:46

100%, so how can I adapt this template to the SARS-Cov-2 study? And, it's so good that because some of the labs are already prepared on how to do immune correlates for Lassa, I basically can adapt. So, that is very, this is the requirement of infrastructure. Some of the hospital staff in those centres have all have been trained on how to do this assay, like the measure the T cell response, measure the Elisa antibody response. So I basically just need to let them know, tweak it to ensure that they understand that this is for COVID. Now, having those infrastructure ready, and also having the collaboration from Cambridge was immensely useful to get this project going.

Ruby 7:43

And it sounds it sounds like yourself, you've seen where these different places -obviously, in Cambridge, they have an established system and you have access to certain wards in the hospital in Nigeria, and it's all about the key core component of sciences about collaboration and it sounds like it's a sort of assembling all of these, different institutions has been amazing in the construction of the project. And in terms of the data that you generate from this, would that be equally collaborative? You know, would it? Do you think it would be informative for people worldwide or, or sort of have longer term implications? Or what what are your thoughts on that?

Chinedu 8:34

I think science is universal, right? Even though location matters, what science is saying is that one plus one is one plus right? So it is definitely gonna be useful while I focus on Nigeria when I was designing this project. So you also consider the human genetics, the race and all those implications in the outcome of results in science. And consider the resources you have as well. So we have limited resources, so it's easier to do that work here. However, there are the results. What will be the outcome of this research? It is to tell you what do you classify as features of protection? So in Nigeria, most of the patients have good T cell response rather than antibody response. If you are administering vaccine you can look for T cells rather than focus on antibody and then see if it is different from what we get. So the body will always respond, the differences won't be much so it will be useful across the group. It's not that the data will be generated here. And part of the work actually, so for example, we do for this advantage of collaboration, what we do for the Lassa work, so what I put for the COVID grant is that we'd measure T cell and antibody response. But we don't have the capacity here to measure the phenotype of T cells. So the T cell is part of the immune cells that helps in fighting diseases. There are different types of T-cell you can have CD4 CD8s, memory T cells. So you need to know which ones are very active. So, if the patient does survive, they've been making effector T cells. I've been making more of memory T cells. So to classify those phenotypes, you need flow cytometry. I don't know if you know flow?. So Flow can tell you, so is the T cell wearing red? Is he wearing yellow? Is he wearing blue? So which one is giving you the actual results? So you know, it's one thing to say this is good, but which type of T cell is the one that is protective? So is it the activated T cell? is it th1 is it th2?. So for the Lassa work that flow cytometry analysis at the single cell level is done in Cambridge. So the COVID work, the funding is not enough to do that part of the work. So the funding can only tell us maybe by an ELISPOT, that a T-cell is responding by measuring the cytokine that the T-cell has produced. So what we intend to do now is to keep the cells and then seek additional funding. And then some of this work on flow cytometry will be done in Cambridge, because I've been in the lab at the Vet School, and we have the capacity to do single cell sorting. So you can stop individual T cells, and then measure the gene profile. So that will be valuable information if you can do it. So hopefully, we'll get funding down the future. The future part of the work will be taking the cells to Cambridge, and then look at them. So we can look at the individual T cells and see what kind of response, to see that makes your work very specific.

Simone 11:57

And in terms of, we're talking now about the kind of future work to follow up this project, but I guess, you know, the fact that it was great that you were able to adapt what you were working on to respond to COVID. But, you know, initially, obviously, we didn't know that we were going to be in this pandemic initially. So in terms of the kind of future work that you were or the things that you were working on before, all this happened. Could you maybe tell us a bit more about that, you were working on lassa fever, but in terms of like your future plans as well?

Chinedu 12:27

So my future plan, now I'm back in Nigeria, I'm hoping to establish a framework for vaccine trials. So I did immunology you know? So I understand that there's this gap, especially for Africans, for us here is that we're not so much involved in vaccine development. So, in vaccine development, there is very little involvement of Africans in vaccine development. So most of the R and D is done in Europe, in Britain in the US and China. However, bulk of the clinical trials are done in Africa. So, and the reason why they always say why not is because of lack of resources, lack of funding, lack of best practice. So what I'm hoping to do for my future work is provide a framework for immune correlates for most vaccines, clinical trials, and also to prepare to get us involved in clinical trials. So it's not just you design Lassa fever vaccine, and we've got Lassa fever endemic in Nigeria, you just administer the vaccine in Nigeria. So I'm hoping to use my research to establish a framework for all these immune correlate studies for most of the infectious diseases. So if you design a vaccine, and we want to do clinical trials here, it becomes collaborative. You know, I can tell you, this is what we know in Africa. This is what we understand about this disease, so without the vaccine. This is what to expect in designing the vaccine. This is what to expect in the outcome of the vaccine. So it's not you don't just go blind in designing vaccines. And with both immune correlate data, I can actually inform you the best way to design a vaccine. So if you are making, you have the resources to design a vaccine for Lassa fever in Nigeria, for example, however you don't. So there are different strains of lassa fever, you have strains 1,2,3,4 and then you're designing vaccine and you design a vaccine that can only target one of the strains. I can inform you from my immune correlate data that the vaccine here is not cross protective. So you cannot use one vaccine to protect for all 4, you need to make individual vaccines. The guys who design a vaccine, who don't have this information can get that provided because I'm here, and the research has to be done here. So if I provide that information to you, then you know how to design the most effective vaccine. And then when you deploy that vaccine here, we also know how to, to get the best the efficacy, the best result from the vaccine, because I already have a template of what should be assessed from these boxes. So my future plan is to fill up that gap, to use my study, understand disease epidemiology, use the platform I have to design a framework for immune correlates of different diseases, and then vaccine clinical trial.

Simone 15:37

And do you think more of that should be happening, if you know if people are working on you know, like if people are working on on diseases that are working for vaccines that where they're doing all the r&d in places where actually you don't have the patients? I mean, one of the things that we've learned from the series of podcasts that we've been doing on Coronavirus is how useful it's been to have the like the science and the actual medicine happening in the same place like in the same building and how that's been really helpful. So do you think maybe, you know, to the future, this could be a kind of moment where we say, okay, maybe from now on we can, you know, or I mean, we should have been doing it from before, but kind of making it really clear that actually, that's something that makes it much easier to or makes the research much more effective if you're doing it in a place where actually it's useful.

Chinedu 16:22

I totally agree. That's the way forward. I know the danger, if you don't do it this way. We won't get any good result, you know? To design a vaccine is very expensive. It's not cheap. You can spend a lot of money doing this thing. If you don't involve the Africans, if you don't involve the people involved in the problem. In the design, you're basically designing this blind design. So the problem which they always identify is lack of expertise. Many of us are here now there are people that I'm hoping that more of us come back and learn the skills. So it's no longer you don't have the skills, people are here who can do this. You've got to involve them. So a good example, most of the big, for this corona vaccine, most of the big companies, or the big funders is the most of the platforms that they are funding now, for me, the shocking thing that will happen is what if that the strain of vaccine in different regions is actually, the strain of the virus in different regions has mutated in such a way that those mutations will affect the effectiveness of the vaccine? You, know, so everything you have funded has been a waste? Because you could have funded vaccine develpoment locally? And if you can find them, collaboration, effective collaboration, I think we move beyond the fact that you some how design a magic answer. Everybody has to be on the table, this is the way it should work. We started learning this lesson from the West African Ebola outbreak, we realised how interconnected we are. It is difficult to make progress when the science happens somewhere and then the recipients are somewhere else, it's never going to happen. It will just be a vicious cycle. Just will be running around the circle. Until we all bring all of us up everybody on board. We all on the same table designing this thing. What I think about health, the concept of health as a basic human right, goes beyond access. Yeah, health as a basic human right. Access is a basic human right. However, equitable distribution of resources and science should be a basic human right. So it's ridiculous to think that people can't think, we can think , what is I think is that we needresources and support. How can you design a vaccine somewhere here, and then you dump it on these people here. So you designed vaccine, majority of the people, you will have access to this vaccine because they have the IMD. They provided everything because they were funded to make this vaccine. And if they get better all you need is this one guy who carries the disease to travel to Africa and then you start again. However, if you share this resources, equally. And then you see that progress is signified progress rather than just focus on progress in one place. If you leave a place left out it will always fall back and affect the progress. And that's my view.

Ruby 19:54

Yeah, no, I think it's an amazing observation and something that we keep finding, because we've been doing quite a few these podcasts and with everyone we speak to the fundamental part of science, should be in collaboration and equally distributed. And equally, everyone should be able to access good quality science and be able to perform good quality science. And yeah, I think this is such such a good example of that. And it does make so much sense that you'd want to develop a vaccine in a place where this disease actually is, it seems so bizarre to sort of take it out of context, and then try and put it back in again. So yeah, thank you for that insight. It's definitely a lot of food for though. Obviously, we're all in different locations. I'm in the UK. Simone is in Spain, you're in Nigeria, so between country to country there's, you know, all sorts of different situations going on. But do you think you could be able to paint a picture of the COVID-19 situation right now in Nigeria?

Chinedu 21:00

Well, I'm not gonna lie, I'm not the expert. You know, like I said, from what I what I what I know, because my lab, the lab here is a centre for diagnosis. So we are somewhat involed. Well, it is not chance, we don't know. But the case fatality in Nigeria hasn't been as bad as it is elsewhere in Europe. We don't know the reason - there are so many hypotheses that could be the reason. So for example, I said today, we've had about almost 1000 cases, confirmed cases and less than 300 deaths. So the mortality rate is still a bit a little bit below 3%, around 3%, because fatality rate is around 3%. This is different from what you see across countries. Some people will say we say Nigeria, the estimated population is 200 million. And we're only done about less than 40 or 50,000 tests. So People are saying we're not testing enough. There could be other factors as well. So we are doing testing. I think the government just lifted the lockdown last two weeks. So partially lifting up the lockdown. So you can go out in the day, there is a curfew, so that you can go from 6-8Pm but then there's curfew. The schools haven't reopened, our borders haven't reopened, so that you can't go from one state to the other. So they're still not, they're still restricted on a state travel. It is a bit a little bit of confusion here and there. But I believe we're doing our best and maybe chance we haven't had too many cases. We haven't had too many fatality. But we do have cases.

Ruby 22:48

And we say thank you so much for speaking to us today. And congratulations again!

Simone 22:53

I think I think that's all we have time for. But we don't take up more of your time.

Thanks for tuning in to this latest episode of BlueSci. We hope that you enjoyed it. And if you want to find out more about Dr Ugwu's work and more about his research in Nigeria, you can click the links in the description of the podcast to find out more. And please remember to subscribe. Leave a review if you enjoyed the podcast if you have any feedback, get in touch with us over Twitter. we are @bluescipod or you can email us at podcast@bluesci.co.uk, or radio@bluesci.co.uk or bluescipodcast@gmail.com. They're all the same email address. So feel free to use either one of them to get in touch with us. And yeah, just see you next time.