Eunice Nduati: Immune responses to HIV
Africa bears the largest burden of infections, and human response influences the general health of the population, when some people have better disease outcomes. By working within our context, we can identify relevant targets for vaccine development, and also understand the immune response we can expect when implementing an intervention.
My name is Eunice Nduati and I work at the KEMRI Wellcome Trust Research Programme in Kilifi, Kenya. I am an immunologist by training, and my area of research involves looking at immune responses to various infectious diseases that are common in the tropics.
My initial work was in malaria, and more recently I have been working in HIV. As an immunologist, my interest is looking at immune responses to antigens, without being particular about what that antigen is. As long as it is one of the big diseases in Africa, which would be HIV, TB or malaria, then I am happy to research it. I look at the host immune responses regardless of what disease it is, because you find that how you respond influences the general health of the population. Finding solutions for the health of people across the continent is my main objective.
The work that we do is largely in basic science; we are interested in understanding immune responses. We know that in a population, there will be people who will be exposed to a pathogen regardless of what that infection is, and some will make responses which seem to have better disease outcome, or that they are protected from the infections, whilst other people will not. We are interested in seeing what those people who are protected or have better disease outcome are doing differently, we are looking for correlates of protection. By being able to identify these correlates of protection, we are able to feed, influence, or inform vaccine development. We helps identify relevant immunogens, which can downstream be used to design appropriate vaccines for the population.
A lot of the research work that has been going in the field has shown waves of certain interests. We had whole seasons when people were very keen on looking for T-cell immunogen for HIV research. More recently we have had people interested in looking at humoral immune responses, which is largely looking at antibody responses. We’ve found that in the last 5-10 years a lot of work has gone into identifying monoclonal antibodies – antibodies which can prevent viral entry to a wide range of viruses, which we call broadly neutralising antibodies. Recently there has been identification of quite a number of these, and even more recently the whole concept of using monoclonal therapy is becoming a reality. Currently there is a trial to try and see whether these monoclonal therapies can be used in the field to protect against HIV. There is currently a large trial carried on in the US, in Brazil and in South Africa. In the coming years we are going to get a lot more important information about where the concept of humoral immune responses will take us in terms of controlling HIV.
The other big thing is the design of new immunogens, the vaccine candidates, and there is a shift towards designing immunogens which have a structure and function that is more similar to the virus that an individual sees. Previously they used monomeric targets which only had one push-on, but now we have more designs of trimeric push-ons. For example BG505, a clinical trial which is going to occur in the US and partly in Kenya, and our work here at the KEMRI Wellcome Trust Programme will be a part of that, analysing what sort of immune responses the vaccinated individuals generate.
I believe that in terms of the actual vaccine, you want a vaccine that is able to work across board. Where you are looking for correlates of protection from the host, you are looking at individuals who are able to make responses that are able to inhibit or neutralise viruses across board. You don’t want a vaccine that is only neutralising clade A in Africa and not clade B in the West, you want something that is going to be across board. This is at the level of the immunogen that you are designing, you want it to be as broad as possible to cover the whole wide range of clades. On the continent you also need to consider other factors that may influence the immune responses – it is one thing to make a good vaccine, but implementing it is equally important, and many things need to be considered at that stage such as environmental exposure, co-infections within the population and genetics. Working in the context of where you are going to use it, you are able to deal with all these other things, or comparing between the two. I don’t imply that you shouldn’t work in other settings, it’s an issue of working within a framework that makes the best of that environment. You may have very advanced technology in one setting, which you should take advantage of, but you may need to consider other factors and combine both and working as a team you are able to come up with a product that not only generates the immune responses that you want, but is also effective.
We work in a very unique setting, in Africa, the continent that bears the largest burden of infections. To control this, we either have to get effective treatments, or effective vaccines. Our work is very basic science, try and understand how human beings respond to these infections. Our work will be influential in terms of being able to identify relevant targets for vaccine development, but more so our work also helps us understand the sort of immune responses that people on this continent are generating, because we know that the environment we are in may influence the immune responses that you generate. For example, in the past we have had vaccines that where very successful in developed settings but not being as effective or efficient when tested in less developed settings. By working within our context we are able not only to identify relevant targets, but also to deal with those other things that will be important to consider if we are going to have an effective intervention.
This interview was recorded in May 2019