Managing malaria

Malaria claimed approximately 6 lakh lives in 2023, according to the World Health Organization. The incidence of malaria is expected to accelerate, as warmer temperatures and altered rainfall patterns due to climate change expand the mosquito's habitat and breeding period. Effective strategies to combat and curb the spread of malaria are therefore now a research priority. A multi-institutional study by Australian researchers has raised hope for a new malaria vaccine that will prevent the spread of malaria by blocking its transmission from mosquitoes to humans.

To live and prosper, Plasmodium, the malarial parasite, cycles in the body of its two hosts — the Anopheles mosquito and humans. When the mosquito bites a person, it injects the parasite, which goes to the liver and multiplies there before entering the bloodstream, where it kills red blood cells, causing fever and chills. A small population of parasites in the form of sex cells also roams in the blood of an infected person. When another mosquito bites the ailing person, it takes up these parasite sex cells, which then fertilise and multiply in the mosquito. This mosquito is then ready to spread malaria to more people through its bite. 

The usual malaria vaccine works by training the immune system to recognise and attack the malaria parasite before it can cause illness. However, the multi-institutional team led by Wai-Hong Tham from the Walter and Eliza Hall Institute of Medical Research in Australia has identified parasite proteins which, if targeted by vaccines, can block the fertilisation of parasites in mosquitoes, curbing the transmission of malaria from mosquitoes to humans. If a mosquito bites an infected person, it will take a transmission-blocking vaccine along with the parasite. This vaccine is designed in a way that it stops parasite fertilisation in the mosquito gut.

"A really attractive stage for transmission blocking vaccines is to target it during fertilisation because parasite numbers are very low in the mosquito midgut compared to in a human during the blood stage cycle," says Tham.

In mosquitoes, two parasite proteins, Pfs230 and Pfs48/45, form a complex that is necessary for fertilisation to take place between parasite sex cells. In their research paper published in the journal Science (bit.ly/transmission-blocking-vaccine), the team, through electron microscopy, found that domains 13 and 14 of Pfs230 are essential for these two proteins to interact and form a protein complex. They further showed that if these domains were mutated, fertilisation did not occur and malarial parasites did not multiply. Hence, a mosquito with such a mutated parasite was unable to pass the malaria parasite to a human.

The team also developed antibodies against these domains and showed that the presence of these antibodies in mosquitoes reduces parasite transmission. The study establishes that these domains are potent targets for transmission-blocking vaccines.

Tham believes that it is important to have vaccines for different stages of a malarial parasite, and an mRNA vaccine that targets different stages — the liver stage, blood stage and mosquito stage — would be useful; domains 13 and 14 of Pfs230 could function as one of the key transmission-blocking vaccine candidates for a multi-stage vaccine.