Researcher of the Month: Innocent Mwape

As part of our work on WASH and vaccines, SHARE supported a study on the immunogenicity of the rotavirus vaccine in infants with environmental enteric dysfunction. We spoke to Innocent Mwape, Bench Supervisor for Virology and Molecular Biology Laboratory at CIDRZ, and first author of the recently published paper in PLOS ONE, to find out more about the results and what they mean.

What is your background?

I did my studies in Russia and then returned home. I joined CIDRZ in 2011. From there I did my first project working on HIV genotyping in infants using dry blood spots. We published in 2015, and then I continued working on HIV genotyping but in adults. Currently I’m a supervisor for the HIV genotyping and molecular biology lab at CIDRZ. I then started my Masters degree in Human Physiology, and did my thesis work on immunogenicity of infants with environmental enteric dysfunction.

What is this study about?

We’ve known that oral vaccines are easy to administer, but there is a challenge when we compare the immunogenicity of the oral vaccine when it is administered in infants in developed countries compared to low and middle-income countries. One of the factors that have been attributed is environmental enteric dysfunction (EED). We wanted to find out how prevalent EED is in our setting. We collected samples from infants who were given the rotavirus vaccine.

Previous work by Dr Roma Chilengi on the efficacy of rotavirus vaccine found that efficacy was about 60%. The same rotavirus vaccine administered in Finland had efficacy of above 90%. We are trying to find the reason why there is a variation.

What were the main findings from your study?

After having collected the samples from 6-8 week old infants who had received the rotavirus vaccine, we group the infants into two groups: those who seraconverted, and those who didn’t seraconvert. After that, we had to test whether they had EED, and we used biomarkers to tell whether they did. We used 4 biomarkers: Zonulin, IFABP, EndoCaB and Soluble CD14. The first two are specific to the infant intestine, so if there is any injury to the intestine, the epithelial cells will release these biomarkers.

What we found was that most of the infants had very high concentrations of Zonulin and IFABP. This led to tell us that most of these infants had EED – it was very prevalent. One of the causes of EED that is hypothesised is that these infants are living in a poor sanitation environment, which leads to them being exposed to enteric pathogens.

Was there anything surprising or unexpected you found?

From our findings, what was really shocking was that the Zonulin and IFABP – the biomarkers that were found in very high concentrations – had a strong positive association with seroconversion. So they are linked with EED but also better seroconversion. These two biomarkers usually test intestinal permeability. It was showing us that the permeability is already compromised at a very young age – they’re taking up everything because of this permeability, even the vaccine.

In the end, what you get is the vaccine looking like it’s performing better because of the overload of the antigens which are going in. But the immune system becomes compromised, so we think in the end you get worse impact later on.

The last two biomarkers showed a negative association, which was straightforward. That’s what we expected to see.

What further research is still needed on this topic?

The last two biomarkers have been used in most studies. But the first two biomarkers haven’t been used in the setup where we used it in the context of the rotavirus vaccine. A paper from Poland showed that most infants infected with rotavirus had very high concentrations of IFABP.

The next logical step would be to have a big cohort of these infants to try to validate the first two biomarkers. It’s not something that we were really expecting, but the explanation is pointing to something that is happening. I think a follow up is needed to validate these biomarkers.