A research team from the Instituto Gulbenkian de Ciência (IGC) led by Miguel Soares has revealed that specific components of bacteria resident in the gut can trigger a natural defense mechanism that blocks malaria transmission.
The key component in the process is a sugar molecule called α-gal (alpha-gal), which is produced by the malarial parasite Plasmodium and also by a strain of the human gut bacteria Escherichia coli. Through experiments on mice, Bahtiyar Yilmaz, a PhD student at the IGC, discovered that the production of α-gal by these bacteria is sufficient to induce the production of natural anti-α-gal antibodies capable of recognizing the same sugar molecule on the surface of Plasmodium.
Immediately after inoculation of the parasite into the skin by the mosquito that transmits malaria, these antibodies bind to the α-gal on the surface of the Plasmodium and activate an additional mechanism of the immune system that kills it before it leaves the skin, preventing it from entering the bloodstream. By doing so the transmission of malaria is blocked.
The level of anti-α-gal antibodies, which research has shown is lower in younger children, may be the differential factor in susceptibility to malaria: only a fraction of all adult individuals actually bitten by mosquitoes become infected, which contrasts with an exponentially higher susceptibility of children under 3 to 5 years of age to contract malaria. An estimated 3.4 billion people are at risk of malaria and WHO data from 2012 indicates that around 460,000 African children died before their fifth birthday.
The research has shown, through experiments in mice, that this protective mechanism can be activated by vaccination against a synthetic α-gal molecule that is relatively easy to produce and inexpensive. As Miguel Soares explains "one of the wonders of the protective mechanism we have now discovered is that it can be induced through a standard vaccination protocol, leading to the production of high levels of anti-α-gal antibodies that can bind to and kill the Plasmodium parasite. If we can vaccinate young children against α-gal, many lives can be saved."
Recently published in the journal Cell, the article gathers the results of the study developed at IGC 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 University of Sciences, Techniques and Technologies of Bamako (Bamako, Mali), and was also funded by FCT, as well as the Bill and Melinda Gates Foundation (USA), and the European Research Council (ERC).