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How do Plasmodium vivax parasites hide from the immune system?

Paolo Bareng is a PhD student in Alyssa Barry‘s group at Deakin University in Australia. He is using MalariaGEN vivax data to hunt for mutations that help parasites evade the immune system. We caught up with him at the American Society for Tropical Medicine and Hygiene (ASTMH) annual meeting. The interview below has been edited for length and clarity.

Blog 1 Dec 2022

 

MalariaGEN: Hi Paolo, thanks for taking the time to chat. Could you tell us a bit about your research?

Paolo Bareng (PB): Sure. My research is about identifying the diversity of antigens in Plasmodium vivax in the context of vaccine development. What I’m doing is trying to identify mutations that are associated with immune escape.

When I say “immune escape,” I mean the ability of the parasite to evade the host immune system. We hypothesise that there are certain mutations — polymorphisms — that make the parasite not easily identifiable by the host immune system. We think that understanding these mutations could guide researchers when they select antigens that will be included in their vaccines.

MalariaGEN: How are you going about it?

PB: I started by looking at the diversity of the antigens, which will provide a foundation to identify these polymorphisms. What that means is that I’m analysing the sequences from different regions of the genome, and looking at diversity. I want to find out which regions of the gene are under immune selection pressure.

MalariaGEN: That’s interesting! How do you know if the parasite is under “immune” selection, or selection from, say, insecticides or drugs?

PB: Good question. There are different kinds of selection that will have different signals in the data. For example, there’s directional selection, which is mostly caused by drug resistance pressure. And that looks different from immune selection pressure, which is what we’re interested in.

We hypothesise that polymorphisms with a low to medium frequency are due to immune selection pressure. This is actually one of the strategies of the parasite. If a polymorphism is common in the population, it will get fixed and then our immune systems will adapt. But if the polymorphism is maintained at a very low frequency, or a low-to-intermediate frequency, it will not get fixed in the population and the parasites can evade our defences. They are very clever!

MalariaGEN: What stage of the project are you at?

PB: I have done the diversity analysis. And after that, I’m going to identify specific polymorphisms associated with immune selection pressure using various genomic assays. My colleague, Myo Naung, actually recently published a similar analysis for P. Falciparum in PLOS Computational Biology. It’s looking promising though. Even in the preliminary analysis, there are some interesting antigens and I’m really interested in looking at those polymorphisms and whether they are under immune selection pressure, or some other kind of selection.


The latest MalariaGEN datasets, including Pv4 — which includes whole genome sequence data from 1,895 P. vivax samples — is available on our Data page.