Human antibodies undermine parasite sex published in Nature Communications

12 February 2018

Some people develop an immune response following a malaria infection that stops them from infecting other mosquitos. The antibodies that these people produce are sucked up by the mosquito and destroy the malaria parasite in the mosquito’s stomach.

Teun Bousema, theme Infectious diseases and global health, and his colleagues discovered that 1 in 25 malaria patients prevent the disease from spreading in this way. They also unraveled the defense proteins responsible, and these could be used to make a vaccine. The results were published in Nature Communications on February 8th.
 
Malaria is a disease that spreads incredibly efficiently. The antimalarial medicines that are currently used cannot do much to stop this, because the parasites remain in the patient’s blood for a long time after treatment. This means that other mosquitos can be infected with the parasite if they bite the patient. The male and female parasites are fertilized in the mosquito’s stomach, the offspring are transferred back to humans when they are bitten by a mosquito, and the cycle starts again. In this way, just one malaria patient can cause more than 100 new malaria infections. In the fight against malaria, it is therefore very important to make sure that people are not able to infect other mosquitos.
 
Altruistic immunity
People who have been infected with malaria produce antibodies. These antibodies can provide protection from further infection, but they can also prevent the spread of malaria as the antibodies destroy the parasites in the mosquito’s stomach, or prevent fertilization. In that case, it is not the patient who benefits from the antibodies that he or she produces, but other people who are bitten by the mosquito. This is therefore an interesting form of altruistic immunity.
 
Malaria researcher Teun Bousema at Radboud university medical center and his colleagues at London School of Hygiene & Tropical Medicine (LSHTM), have discovered that 1 in 25 malaria patients are able to stop malaria spreading in this way. Amongst missionaries who had been infected with malaria dozens of times during their missionary work, immunity was even more common. Bousema: “This is the first time that we have been able to produce direct evidence that human antibodies against malaria parasite proteins are able to prevent the spread of malaria.”
 
Vaccine to halt spread
Research into whether people can stop the spread of malaria is incredibly labor-intensive. For each patient, dozens of mosquitos need to be investigated to see whether they have been infected after sucking up the blood of the malaria patient. Until recently, all these mosquitos needed to be dissected. Luckily, however, this problem has now been solved. Bousema: “We have developed a malaria parasite that expresses a firefly gene, allowing us to see just by looking at the mosquito whether or not it has been infected.” This has sped up the research considerably.
 
PhD student Will Stone studied people’s immune response to over 300 malaria proteins.  Stone: “We saw that our test subjects produced antibodies that are able to slow the spread of malaria in response to 45 of these proteins. People with these antibodies were ten times less likely to infect mosquitos.” Stone will defend his thesis about this research on February 22^nd at Radboudumc and will continue his research at LSHTM. Bousema: “This research enables us to better understand which patients prevent the spread of malaria. We are now looking at whether it is possible to develop a malaria vaccine using some of these proteins. A vaccine that prevents the spread of malaria would help reduce the disease burden of malaria worldwide.”

Publication:
Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity
Stone WJR, Campo JJ, Ouédraogo AL, Meerstein-Kessel L, Morlais I, Da D, Cohuet A, Nsango S, Sutherland CJ, van de Vegte-Bolmer M, Siebelink-Stoter R, van Gemert GJ, Graumans W, Lanke K, Shandling AD, Pablo JV, Teng AA, Jones S, de Jong RM, Fabra-García A, Bradley J, Roeffen W, Lasonder E, Gremo G, Schwarzer E, Janse CJ, Singh SK, Theisen M, Felgner P, Marti M, Drakeley C, Sauerwein R, Bousema T, Jore MM.
Nat Commun. 2018 Feb 8;9(1):558.


Teun Bousema
 

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