Boosting our natural antibody responses against the transmissible parasite stage could hold the key to combatting the malaria parasite and preventing the spread of the disease. It was previously though thought the human part of the malaria transmission cycle is immunologically “silent”. However, a new study demonstrates that natural immune responses can recognize and kill parasites in this phase of the life cycle before they can spread to mosquitoes.

In the new research, published today in Science Translational Medicine, scientists have revealed previously unknown targets of natural human antibody responses that are found on the surface of the red blood cells infected with malaria parasites. The team behind the study believe that using a vaccine to boost this natural response may provide an efficient way to block both disease and its spread.

Malaria remains a significant threat to human health with approximately 216 million cases annually and over 400,000 deaths worldwide. Of particular concern are the recent rebound in cases over the past year, mostly in sub-Saharan African and South America and the spread of artemisinin-resistance from Southeast Asia.

Malaria is caused by the Plasmodium parasite that depends on mosquitoes and humans for its transmission. When an infected mosquito bites a human, it injects parasites that make people sick and sometimes lead to death. Some of the pathogenic parasites develop into transmissible forms that can then be taken up by another mosquito. Part of that parasite development takes place in red blood cells in the bone marrow.

Previous research combatting transmission of malaria has focussed on the mosquito stage of the parasite’s lifespan. Scientists believe these new findings offer an alternative, and potentially highly efficient route to preventing disease spreading.

The research – which was led by the University of Glasgow in collaboration with Radboud University Medical Center, The Netherlands and Harvard University – studied human plasma samples from over 500 infected individuals from Cameroon, Burkina Faso, the Gambia and Malawi.

The study discovered novel antigens that were attached to the surface of the infected red blood cell at two different parasite stages of its lifespan in the human body, the replicative asexual stage and the transmissive gametocyte stage. The scientists then went on to reveal that the human body produced natural antibodies in response to these antigens, and that increased levels of some of these antibodies were associated with reduced asexual stage and gametocyte burden during malaria infection.

Gametocytes are the only parasite stage capable of transmission to the mosquito and hence essential for the spread of the disease. The immune response that was newly discovered reduces both asexual multiplication and the maturation of transmissible gametocytes.

Professor Matt Marti, from the University’s Institute of Infection, Immunity and Inflammation, said: “This is a significant development in our need to find a plausible target for a malaria vaccine against the human blood stage forms of the parasite. Targeting antigens that are present both on asexual and gametocyte stages may reduce disease and transmission in one hit.

Prof Teun Bousema from the Radboud university medical center, indicates that “Whilst there is no single magic bullet that solves malaria, this is a very promising discovery. It helps us in understanding how malaria spreads in communities and offers an important new lead to develop novel tools. Such novel tools are critical to maintain the momentum of the ongoing malaria elimination campaign and finding new ways to end the spread of this awful disease”

The study, ‘Naturally acquired immunity against Plasmodium falciparum immature gametocytes’ is published in Science Translational Medicine. The work was funded by Wellcome, the US National Institute of Health, the European Research Council, Bloomberg Family Foundation through the Johns Hopkins Malaria Research Institute, the Netherlands Organization for Scientific Research, Swiss National Science Foundation, the American Heart Association and the Agence Nationale de la Recherche.

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First published: 5 June 2019