Blood from a missionary and a Ugandan girl offers the prospect of better malaria vaccines

The blood of a Dutch missionary and a young girl from Uganda offers leads for a new vaccine against malaria. Nijmegen researchers discovered antibodies that render the malaria parasite infertile. They published there with a team of international colleagues two studies over, Tuesday in the science journal Immunity.

Malaria is a tropical disease. The most dangerous and common form, malaria tropica, is caused by the parasite Plasmodium falciparum. It is transmitted to humans when bitten by female Anopheles mosquitoes. Initially, someone gets feverish attacks, headache and muscle aches. But that can quickly turn into a phase with deadly complications. Treatment is only possible at an early stage. A major problem is the increasing resistance of the parasites to antimalarials. Every year 620,000 people die from malaria, mainly young children and pregnant women.

Read also: Three blows for drug-resistant malaria

Malaria vaccines are therefore being sought diligently, but they are difficult to make. So the scientists examined the blood of people who naturally have a strong defense against the disease. Most people living in malaria areas build up immunity over the course of their lives.

The missionary’s blood had been in the freezer for thirty years

Support Bousema Radboudumc

“The blood of the missionary with the strong immunity had been in the freezer for thirty years,” says epidemiologist Teun Bousema of Radboudumc, one of the study leaders. They discovered the blood of the eight-year-old girl in a long-term study of 500 people in Uganda. “In her blood we saw a strong immune response month after month, which is very rare.”

The researchers looked at where in the complicated life cycle of the parasite the immune system intervened so successfully. After an infection, germ cells of the parasite end up in red blood cells. A mosquito sucks up that infected blood, which produces male and female germ cells (gametes) in its stomach. They fertilize each other, and via the saliva of the mosquito, the parasites end up in the next person after a bite.

**A cultured mosquito** from the Nijmegen experiment pierces through a piece of fake skin.
Photo Teun Bousema/Radboudumc

Bousema and his team tested hundreds of blood samples. Farmed mosquitoes in small cages could pierce a piece of fake skin to eat the blood offered. Two samples had a striking effect: when mosquitoes ate samples of blood from the missionary or girl mixed with parasites, the parasites could not spread further.

Parasitologist Matthijs Jore discovered more than a hundred antibodies against a surface protein of germ cells and gametes and against another protein that is important for fertilization. These were found to block the fusion of the female and male gametes in the mosquito’s stomach. For example, the mosquitoes could no longer pass on the parasite with a bite.

Further research by Jore and his colleagues revealed that the most potent antibodies were mainly directed against specific parts of those proteins. Jore: “Now we know against which domains of those proteins we have to develop new vaccines, and which ones we should leave out.”

mosquito nets

Since 2000, substantial investments have been made in malaria research, in particular by the Bill & Melinda Gates foundation. There was also more information about the use of mosquito nets and mosquito repellent measures. This reduced the number of deaths from malaria. But since 2015, the number of malaria cases has been rising again in many countries.

There is a vaccine (RTS,S) that has been widely used in children for a few years. It is directed against the parasite form as it is injected by the mosquito. Bousema: “It mainly prevents a person from becoming ill, but it inhibits the distribution of the parasite. A mosquito that bites them will still ingest the parasite. And the vaccine only works to a limited extent: it offers three years of protection for a third of the vaccinees.”

People with natural immunity can also spread the parasite, says Bousema. “A vaccine that prevents the spread is therefore desperately needed.”

The Nijmegen discoveries are a big step towards a vaccine that can prevent the spread, because it prevents the parasite from developing in the mosquito.

Bousema: “Resistance is a major problem with malaria. It is likely that resistance to the existing vaccine will also develop. That is why we believe in a combination with a vaccine that prevents transmission.”