An nCounter® in The Gambia: An interview with Tuberculosis Researcher Jayne Sutherland

NSTG: Jayne, it’s so lovely to meet you. Could you tell us about your background and your research interests?

Jayne Sutherland: I’m an immunologist by training; for my Ph.D., I studied cancer. I’m from Australia, and I did my Ph.D. in Melbourne, moved to London, did another couple of years of post-doc after my Ph.D. Eventually, I met Prof Sarah Rowland Jones from Oxford, who was about to do some HIV work in the Gambia; she put me in touch with a job opening for a research position studying tuberculosis (TB). I knew nothing about TB, but it was all about immunology, so I decided to apply for the job and moved to The Gambia 15 years ago.

I’ve been working on TB ever since. Being based in The Gambia doing TB research, I feel like I’m impacting patients directly instead of being so far removed in a lab.

NSTG: You started in cancer immunotherapy, and that’s all about the immune system. Are there any lessons learned from cancer research and immunotherapy that also apply to infectious disease?

Jayne: Both look at similar cell subsets. The principles and the pathways are not going to be the same, but the techniques and how you do experiments and analyze the data are relevant to both fields. It does mean you can change your field of research. Technically, it would help if you still learned all the background research and how different cells play different roles in other diseases. TB is a very tricky disease because some people get infected for their lifetime yet never actually get the disease. This is a significant group of patients to study so we can work out why they never get the active disease.

Probably COVID-19 research is more relevant; the rapid progression of research diagnostics, therapeutics, vaccines happening with COVID shows us what can be done if the world takes an interest in TB.

NSTG: TB is a disease that’s rarely talked about in the United States or in Australia. As you mentioned, it typically responds well to antibiotics if caught quickly. What remains to be uncovered about this disease?

Jayne: So much! The interesting thing with TB is that we still don’t know how people can be protected. This is because infected people initially don’t show symptoms.

A blood test shows they have been exposed, but not if they have the bacteria. Disease progression and activity happen between 12 and 24 months. Moreover, only 3% to 5% of people infected will get the disease, making it hard to recruit high enough numbers of research subjects to understand why some get the disease and others don’t.

We still don’t understand what protects people from getting active disease. There’s a whole community of researchers looking at the lung and blood. They’re trying to develop a vaccine and figure out what parts of the immune system the vaccine should target for protection. At this moment, the only licensed vaccine has limited efficacy. It has some protection in children, but it certainly doesn’t protect adults from TB. 

Unfortunately, antibodies are not the main indicator of protection against TB. We know with COVID-19 vaccines, for instance, if you get enough antibodies, you will be protected from getting severe disease. That’s not the case for TB, at least for later stages of the disease, making it tricky to design vaccines.

Prevention – and Early Diagnosis – is Better than Cure

NSTG: You touched on this earlier when you mentioned drug resistance. It’s our understanding that drug-resistant TB is beginning to be a big problem. Could you tell us how your work might help understand drug-resistant TB a little bit better?

Jayne: Yes. We don’t do a huge amount of work on drug-resistant TB because we don’t have high levels of it in The Gambia. We have good compliance programs to ensure patients take their treatments and avoid developing drug resistance. 

In terms of how my work can help with drug-resistant TB it’s more about if we can get people diagnosed and vaccinated. Suppose we can get people diagnosed early on. In that case, there will be less transmission and less likelihood of developing drug-resistant TB or, at least, less possibility of transmission of drug-resistant TB. My work helps us block this transmission pathway, preventing it from infecting other household members.

NSTG: How long has the London School of Hygiene and Tropical Medicine been working in the Gambia?

Jayne: The UK’s Medical Research Council (MRC) has had a site in the Gambia for 75 years.

 They established it because they wanted to research tropical infectious diseases such as malaria. Although scientists and facilities are available in England, these diseases are not endemic to the UK. It made more sense to bring the research to African countries to be closer to the frontline regarding certain infectious diseases. The research facility in the Gambia was established 75 years ago. There were always links to the LSHTM, but we became permanently part of the LSHTM four years ago. 

Before that, the laboratory was purely affiliated with the MRC. They used to fund all our research. Then the funding structures changed a little bit. We became part of the LSHTM in 2018.

NSTG: This is interesting! Is the laboratory you work in also affiliated with local institutions and universities in the Gambia?

Jayne: Yes. We have an affiliation with the University of the Gambia. I don’t think it’s even 20 years old. It’s quite new. We have a lot of students that come through from the university. 

NSTG: Can you tell us more about the TB case contact cohort?

Jayne: This was established before I arrived. It allows us to diagnose someone with TB and to visit their close contacts. After informed consent, we take blood samples from them up to 2 years from enrollment to identify the immune cells that protect people from getting active disease. This information can help inform vaccine design. We identify the TB case either at the MRC clinic or through outside health clinics. After obtaining consent, we go to the house and recruit patients into our research program whether they are kids, adolescents, or adults; we assess them, do symptom screening, and look at their immune profiles.

We hope to translate this research into identifying upfront whether a patient has a certain gene signature and assess based on whether they are at risk of developing active disease and should go on prevention. There are a lot of avenues open once you work out what’s happening with the immune system and distinguish between people who get active disease and those who don’t. Those who don’t get active disease can help us identify what kind of immune response a vaccine must induce to provide protection. I’m particularly interested in the early stages of infection, both in the blood and the lung. 

When people are exposed, what immune cells are activated and recruited? We know they’re going to be different between individuals with active disease versus those without disease. We’re hoping antibodies might play a role as well in which case you could give a vaccine to people who are not infected and see if you can prevent infection as well as disease. Currently, TB vaccines are mainly designed to protect people infected from getting active disease. There are many different ways we utilize the data from the TB case contact study. There’s also social science, health economics, and lots of other different arms of science that work together.

Gaining People’s Trust

NSTG: You touched on something that we wanted to ask you about: cultural reception to disease. Treating disease and preventing it can be challenging in certain cultures where people who have the disease are reluctant to see a doctor and are actively shunned by their families. Do you see some of these cultural challenges working in The Gambia? Also, what are some of the unique challenges that face TB patients in The Gambia?

Jayne: Stigma is a big issue associated with infectious diseases and TB that comes from misinformation. We actively participate in community meetings where we try to dispel some of the myths around TB and emphasize the importance of seeking treatment. We must do it carefully. However, the MRC has an excellent reputation, and people are receptive to our work and education.

I think this is where social science plays a big role. Before we do any studies, we have community meetings, and we are upfront about what we’re trying to do. The community can ask questions at these meetings. We also try not to be too obvious when we visit the households. There can be issues with landlords. Landlords have been known to evict tenants if they find out that someone renting from them has TB.

There’s a lot that goes on that we try to overcome, but a lot of it is just a matter of education. Part of our mandate is that we have a community engagement platform with our projects.

NSTG: Do you sometimes partner with community members to help recruit people into the study?

Jayne: We do it to a certain extent. It’s not official, but we will approach the elders of the community, for example, and tell them about a study that we are doing. Then they will hopefully disseminate the information to the community directly and act as a liaison between the community and the MRC. If there are any issues, we are kept informed and can address them immediately.

Also, they can inform us before we even start the study to make us aware of any issues in the community. The TB study is a bit different from other studies that we have done; we are mainly doing non-interventional trials. Hopefully, we will be one of the sites for the new Phase III vaccine trial. That will be the first interventional trial we’ve done for a long time. We need to emphasize how important it is to get blood samples even when people aren’t feeling sick because, in this way, we will see how effective the vaccine is.

There has been the same level of vaccine hesitancy here with COVID-19 vaccines as everywhere else, but I’ve got to say that when it comes to children being vaccinated, it’s rare for families to be hesitant. They can see what the level of disease is here. They see that kids die without having these vaccines. For example, the kids here have more vaccines than they get in the UK. The level of under-five mortality is quite high. When you talk here about making a new vaccine, trying to get rid of this disease, the urgency is understood well.

NSTG: This is a good segue into the next question. What are the options for TB treatment and vaccines, particularly in the developing world, such as in the Gambia?

Jayne: We have the same access as the rest of the world. For example, let’s talk about the TB vaccine. The only one available is Bacille Calmette-Guérin (BCG) That’s given at birth here as in most countries where TB is endemic. We are lucky that the government provides BCG. 

Treatment is free of charge; when we do community engagement, we make sure that people know that TB treatment is free. We have been doing health economic evaluations for the last five or six years. There are health economic implications for people who have TB because they can’t work for some time.

After starting treatment, most people can return to work after a few weeks. We know that the level of bacteria in the body goes down substantially once you are being treated. You won’t be transmitting, but the problem is people wait too long to come and get the treatment. By the time they wait five months, their lungs are damaged, and they never quite recover properly. Again, we try to educate them about this and make sure they seek treatment early on. 

An Effective Vaccine for Tuberculosis

NSTG: You mentioned earlier that there’s a new vaccine in Phase III trials. Could you tell us more about the vaccine?

Jayne: A Phase III trial is starting sometime this year. There are different vaccines, and many of them target different aspects of TB, like infection or disease post-treatment. This one, M72, has been shown to have 50% efficacy against disease in a South African study. The Gates Foundation is funding the Phase III study, which will consist of 50 different sites. Initially, we will recruit 8,000 patients and then 16,000 participants for the actual Phase III trial.

The first phase of the study involves a screening to make sure we’re targeting the right population. The second phase is a randomized trial with the vaccine. Because TB progresses slowly, we won’t know the endpoint for 12 months or longer.

NSTG: Can you tell us a little bit about the vaccine itself? 

Jayne: The M72/AS01E candidate vaccine (GlaxoSmithKline) contains a recombinant fusion protein derived from two M. tuberculosis antigens (Mtb32A and Mtb39A), combined with the AS01E adjuvant system. The crucial element is: which specific antigens of the pathogen are targeted.

The First nCounter in West Africa

NSTG: Switching gear, how did you first learn about the nCounter® Analysis System, and what appealed to you?

Jayne: I first heard about it from my colleague in South Africa, Tom Scriba. Scientific research is so expensive, but it’s even more costly when you’re in a country like the Gambia where you don’t have access to many technologies. You must outsource a lot of things. In the United States, there are designated sequencing facilities, and funding for these cores offsets the cost for NGS, but we don’t have that here. 

We’re lucky with the MRC in that at the end of each year. We can request funding for equipment for specific projects. That’s how I put in a bid to get the nCounter, and we luckily got the funding! I think this is the first nCounter in West Africa.

NSTG: Yes, we believe it is!

Jayne: The benefit of targeted expression analysis with the nCounter is easier data analysis. It’s all well and good to generate massive datasets with whole transcriptome RNA sequencing, but you’ve got to have the ability to analyze it. My two students who have done the assay so far have received a lot of help from NanoString® and said that the nCounter is quite user-friendly and the analysis is straightforward. It’s helped them, so we have seen a lot of positives.

NSTG: Great! We love to hear that. We think the nCounter is particularly suited for certain countries in Africa or other places where access to funding and skilled technicians is scarce. The nCounter requires only 15 minutes of hands-on time. It’s so simple to run, and the analysis is quite straightforward. We would love to replicate your experience with the institute in The Gambia with other places in Africa. How do you plan to use the nCounter system? Are you developing a Custom CodeSet, or are you using an off-the-shelf panel?

Jayne: Currently, we’re using an off-the-shelf panel, but the plan in the future is to use off-the-shelf panels to discover important biomarkers and then switch to Custom CodeSets once we’ve narrowed down on a set of genes.

We’re using the nCounter to look at treatment response markers for TB. The standard for treatment is six months, but some people may not start out with a high level of bacteria and can get by with only two months of treatment. The only way to know this is to do a sputum culture, which takes six weeks to get a result. Suppose we can instead use biomarkers in the blood to ascertain this. If you can do a finger stick blood test that tells you whether someone is culture-negative –we can personalize each person’s treatment regimen and cut down on treatment time. 

NSTG: Do you feel that having the nCounter system in your lab gives you an advantage over other African infectious disease research labs? 

Jayne: It’s not just the ability to get the result; it’s the capacity that we are building. We try not just to be a sample bank. We really try not to send the samples outside but rather train people on the ground to be able to do the experiments and the analysis. Otherwise, you’re never going to change that culture. Having the nCounter in the lab has been fantastic in capacity building here. It has given us autonomy in addition to the capacity. It’s been a great asset.

NSTG: Excellent! What are some of the challenges facing biotechnology research labs in a developing country that our readers may not be aware of coming from countries and institutes with access to most everything?

Jayne: There are all sorts of challenges here. First, we are a country with ten power cuts a day, which hasn’t changed for years. We discussed this as a lab the other day, and we think it’s getting worse. If you have ten power cuts a day and you’re trying to run expensive equipment, this is impossible. We’re lucky that at the MRC, we have solar power and decent generators that will keep the equipment going. Then you’ve got to have enough computing and internet bandwidth, especially for full sequencing. We do whole genome sequencing where even more computing capacity is required in addition to the internet capacity. We’re so fortunate that we have high-speed internet at the MRC and again the constant power supply with access to generators.

We have fantastic equipment because we get these equipment grants to acquire new technologies. Outside the MRC, when you go to some hospitals, some of the doctors might be operating when the power goes out. It’s a developing country. You’ve got to be aware of limitations. Our most significant limitation is expertise on the ground because you get brain drain here, which is understandable.

NSTG: Do people want to study and leave to go abroad?

Jayne: My brilliant Ph.D. student from Cameroon has got a fantastic post-doc job in America. Of course, he needs to go and do that, but we try and get people to come back eventually. You’ve got to have funding for post-docs, and there’s very little funding for those early career researchers. I think it’s a problem all over. We also don’t have bioinformatics support. If you think of it there is a human side to research and the technology side.

Here you have to think about what happens if an instrument stops working. Thankfully, we haven’t had that issue yet with the nCounter. If you are in Europe and an instrument in the lab breaks, the engineer will come within a day, maybe two days. Here this is not the case; however, we have a biomedical engineering facility on site, which is fantastic because at least we have a first line of support to help get things up and running again.

NSTG: It sounds like with all these challenges, having a generator notwithstanding, it seems like the nCounter system is a great fit; the fact that it’s automated, you don’t need a lot of expertise to run it, the analysis is super easy. Thanks so much for chatting with us, Jayne. We’re going to wrap up with just one question: you have been given a unique opportunity to see a different culture that many of our readers have never been exposed to. Can you tell us about the most memorable experiences living in The Gambia?

Jayne: What I love the most, which is probably why I stay here, is that people are always willing to jump in and help. For instance, my very old car broke down once, and immediately people were there who wanted to come and help. It wasn’t about getting money or anything. It was just about making sure that I was going to be okay.

Considering how poor people are, if you need anything, people will offer you what they can. It’s unusual to see someone not eating enough because people will share whatever they have: It’s a part of their culture, and they want to share their rice. I love this aspect of the culture. 

NSTG: It was so lovely talking to you, Jayne! Thank you for sharing your nCounter in the Gambia with us!

Jayne: You’re welcome! Thank you for speaking with me.

For Research Use Only. Not for use in diagnostic procedures.