Natural antibodies provide blueprint for malaria vaccine Insights in natural immunity thanks to girl from Uganda and Dutch missionary

The blood of a Dutch missionary and a girl from Uganda form the basis for new vaccines against malaria. Naturally acquired antibodies from their blood can prevent the spread of malaria parasites via mosquitoes. An international research team mapped these antibodies and their mechanism of action in detail. The results are described in two publications in Immunity.

It's very rare, but some people's blood can block transmission of malaria parasites, preventing the spread of the disease. How do you track these people and what is in their blood? The team of epidemiologist Teun Bousema at Radboud university medical center developed a test for this: they mix the serum of people who may be immune with cultured malaria parasites and feed it to a cage of mosquitoes. Occasionally, it turns out that the serum prevents transmission of parasites via mosquitoes.

‘We screened serum of hundreds of people this way, mostly from Africa. They had all been exposed to malaria’, says Bousema. ‘In the end, two of them showed very strong and long-lasting immunity to mosquito-infecting parasites: a Dutch missionary, whose blood had been in the freezer for 30 years, and a little girl from Uganda.’ Researcher Matthijs Jore then continued with an international team to unravel which substances in the blood are so special that they prevent the transmission of the malaria parasite.

Vaccine against transmission

The research team found more than a hundred antibodies in the blood of the missionary and the girl that could play a role in their strong defenses against malaria. Antibodies are products the body makes that are very specifically directed against a foreign substance, in this case against two different proteins on the malaria parasite that are important for transmission via mosquitoes. ‘We tested all those antibodies separately from each other in the lab; which antibodies prevent parasite transmission to mosquitoes, and which antibodies do nothing?’ says Jore. ‘All those antibodies contain important information for a vaccine against malaria.’

Jore and his team studied the antibodies in great detail, together with colleagues at The Hospital for Sick Children in Toronto. He examined not only which proteins they targeted, but also which part of the proteins. Jore says: ‘We saw that the most potent antibodies were directed against certain parts of the proteins, while non-functional antibodies bound other parts. We are now using this information to develop a new vaccine against the spread of malaria.’

Protecting young children

New efficacious vaccines against malaria are urgently needed. Despite many investments and efforts, 600,000 people die of malaria every year, especially young children. ‘Transmission of malaria via mosquitoes is very efficient: one person can infect as many as one hundred other people. Preventing transmission is therefore an essential component in malaria contro’, says Jore. ‘Our results are a big step towards the development of an effective vaccine against the spread of this disease. Our new insights in the naturally acquired immunity of the missionary and the girl from Uganda may to be the key to success.’

About the publications

The results were published in Immunity:

Highly potent naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes. Amanda Fabra-García, Sophia Hailemariam, Roos M de Jong, Kirsten Janssen, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Danton Ivanochko, Anthony Semesi, Brandon McLeod, Martijn W Vos, Marloes HC de Bruijni, Judith M Bolscher, Marta Szabat, Stefanie Vogt, Lucas Kraft, Sherie Duncan, Moses R Kamya, Margaret E Feeney, Prasanna Jagannathan, Bryan Greenhouse, Koen J Dechering, Robert W Sauerwein, C Richter King, Randall S MacGill, Teun Bousema, Jean-Philippe Julien, Matthijs M Jore.

Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230. Danton Ivanochko, Amanda Fabra-García, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Jocelyn Newton, Anthony Semesi, Marloes de Bruijni, Judith Bolscher, Jordache Ramjith, Marta Szabat, Stefanie Vogt, Lucas Kraft, Sherie Duncan, Shwu-Maan Lee, Moses R Kamya, Margaret E Feeney, Prasanna Jagannathan, Bryan Greenhouse, Robert W Sauerwein, C Richter King, Randall S MacGill, Teun Bousema, Matthijs M Jore, Jean-Philippe Julien.

Financial support for this study was provided by PATH’s Malaria Vaccine Initiative and the Bill & Melinda Gates Foundation.

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