A research team led by Miguel Soares at the Instituto Gulbenkian de Ciência (IGC) discovered that specific components of bacteria that live in the human gut trigger a natural defense mechanism that is highly protective against malaria transmission.
The key component is a type of sugar molecule called α-gal, which is produced by both the Plasmodium parasite, that causes malaria, and a strain of the bacterium Escherichia coli that is part of the human gut microbiota (the community of harmless bacteria that inhabit the gut). In a series of experiments performed in mice, Bahtiyar Yilmaz, a PhD student at the IGC, found that expression of α-gal by these bacteria is sufficient to induce the production of natural antibodies that can recognise the same sugar molecule when expressed at the surface of Plasmodium parasites.
Immediately after inoculation of the parasite in the skin, via a mosquito bite, these antibodies attach to the α-gal sugar on the surface of Plasmodium parasites and activate an additional arm of the human immune system, which kills the Plasmodium parasite before it can move out of the skin. This arrests the transition of the parasite from the skin into the blood stream and in so doing, blocks malaria transmission.
Only a fraction of all adult individuals that are bitten by mosquitoes in areas where malaria is endemic become infected by the Plasmodium parasite and eventually go on to contract malaria. This is in sharp contrast with children under the ages of 3 to 5, that are much more susceptible to malaria. The reason for this difference may be due to the fact that they have not yet generated sufficient levels of circulating natural antibodies directed against the α-gal sugar molecule. It is estimated that 3.4 billion people are at risk of contracting malaria and WHO data from 2012 reveal that about 460 000 African children died from malaria before reaching their fifth birthday.
Bahtiyar found that when mice are vaccinated against a synthetic form of α-gal that is rather easy and inexpensive to produce, they produced high levels of circulating anti-α-gal antibodies that are highly protective against malaria transmission by mosquitoes.
Miguel Soares adds: “We observed that children under 3 years old do not have sufficient levels of circulating anti-α-gal antibodies, which might be one of the reasons for their exquisite susceptibility to malaria. One of the beauties of the protective mechanism we just discovered is that it can be induced via a standard vaccination protocol, leading to the production of high levels of anti-α-gal antibodies that bind and kill the Plasmodium parasite. If we can vaccinate these young children against α-gal, many lives might be saved.”
This study was carried out at the Instituto Gulbenkian de Ciência (Oeiras, Portugal) in collaboration with the National Institute of Allergy and Infectious Diseases (Maryland; USA), Instituto de Higiene e Medicina Tropical (Lisbon, Portugal), St Vincent’s Hospital and University of Melbourne (Victoria, Australia), University of Chicago (Chicago, USA), and the University of Sciences, Techniques and Technologies of Bamako (Bamako, Mali). This research was funded by the Bill and Melinda Gates Foundation (USA), the Fundação para a Ciência e a Tecnologia (FCT, Portugal), and the European Research Council (ERC).