Malaria was the cause of around 627,000 deaths worldwide in 2012, with 90% of these deaths occurring among children under the age of 5 years living in Africa. Now – in what is described as a “breakthrough” in malaria research – scientists have discovered specific bacteria in the gut that may induce a natural defense against the infection.
The research team, led by Miguel Soares at the Instituto Gulbenkian de Ciência in Portugal, publish their findings in the journal Cell.
In recent years, researchers have learned more about the “friendly” bacteria that live in the human gut, known as gut microbiota. Rather than cause disease, these bacteria can trigger immune functions that protect against it.
Studies have shown that in adults, certain strains of Escherichia coli bacteria that live in the gut can protect against disease by expressing sugar molecules, or glycans, from their surface.
The immune system recognizes these glycans and, in response, produces large numbers of natural antibodies that circulate throughout the body, staving off infection.
In this latest study, Soares and his team found that the parasite that causes malaria – Plasmodium – expresses a sugar molecule that is also expressed by a friendly strain of E. coli – called alpha gal (α-gal).
When α-gal from E. coli was expressed in the guts of mice, it caused the immune system to produce natural circulating antibodies that recognized α-gal expressed by Plasmodium parasites immediately after a bite from a mosquito.
Upon recognition of the α-gal expressed by Plasmodium parasites, the anti-α-gal antibodies produced by the immune system triggered what is called the “complement cascade” – a part of the innate immune system that kills pathogens. This process killed the Plasmodium parasites, preventing malaria transmission.
Only a small number of adults who are bitten by mosquitoes go on to develop malaria, while children under the age of 5 years appear to be much more susceptible to the infection. Could this be down to levels of circulating anti-α-gal antibodies produced by the immune system in response to the Plasmodium parasite? The researchers wanted to find out.
In collaboration with researchers from the National Institute of Allergy and Infectious Diseases in the US and the University of Sciences, Techniques and Technologies of Bamako in Mali, Soares and his team analyzed the gut bacteria of individuals from an area of Mali with high malaria transmission.
They found that people who had the lowest levels of circulating anti-α-gal antibodies were much more susceptible to malaria than those who had the highest levels of these antibodies.
The researchers say this finding suggests that young children may be much more susceptible to malaria because they do not produce circulating anti-α-gal antibodies at high enough levels to stave off malaria infection.
The team went on to develop a vaccine in the form of synthetic α-gal antibodies and tested it in mice to see how effective it was against malaria transmission by mosquitoes.
They found the vaccine increased production of circulating anti-α-gal antibodies in the mice and was highly effective in protecting the rodents against malaria infection. The researchers are now hopeful that the vaccine has the same effect in humans.
Commenting on the team’s findings, Soares says:
“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.”
In September, Medical News Today reported on a study published in Nature Genetics suggesting that the severity of malaria may be influenced by five human genes.