Scientists discover new antibodies - a promising target for clinical exploration.

Transcript

The currently licenced malaria vaccines and monoclonal antibodies all target a well-known region of the same malaria protein. That protein – the circumsporozoite protein, commonly known as CSP – covers the surface of the parasite as it enters the human skin through a mosquito bite. By targeting CSP, the vaccines aim to stop each malaria parasite in its tracks. But what about other proteins on the sporozoite - the parasite form injected into the blood by the mosquito - or other regions of the CSP protein? In a recent study, scientists screened plasma from malaria-infected individuals for immune responses against sporozoites. Many had developed antibodies against these well-known regions of CSP, but some had developed antibodies targeting a different region of the sporozoite surface. Out of ten new antibodies isolated from these individuals, several were functional – inhibiting the development of later parasite stages that occur in the liver and preventing sporozoite infection in a mouse model of malaria. However, they were targeting a different region of CSP that was only uncovered after processing by the sporozoite. This new region – called pGlu-CSP – is, the authors say, a site of vulnerability and a promising target for future clinical exploration.

Source

Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein (Science)

About The Podcast

The Johns Hopkins Malaria Minute podcast is produced by the Johns Hopkins Malaria Research Institute to highlight impactful malaria research and to share it with the global community.

We focus on drug resistance and the troubling news that the frontline drug against malaria, artemisinin, is failing due to resistant parasites in severe cases of malaria, and how the collective efforts of drug development – and the data produced – could be used to build an AI chatbot capable of predicting resistance before it strikes.

With Robert Opoka and Elizabeth Winzeler.

About The Podcast

The Johns Hopkins Malaria Minute is produced by the Johns Hopkins Malaria Research Institute to highlight impactful malaria research and to share it with the global community.

Researchers search for ways to predict antimalarial drug resistance and identify more effective drug combinations.

Transcript

The front-line treatment for malaria is typically a combination of drugs called artemisinin-based combination therapy. Resistance to treatment has already been reported in mild cases of malaria, but now, for the first time, it’s also being reported in severe cases of malaria. Severe malaria cases are more likely to end in a fatal outcome, so drug resistance in these scenarios poses a risk to human life. To try and stay one step ahead of resistance, researchers tested compounds and combed through publications to identify 118 compounds active against over 700 parasite clones to see how the parasites evolve under pressure, and to identify mutations in the parasite genome likely to be associated with drug resistance. They confirmed that Plasmodium falciparum – the deadliest and most prevalent species of the malaria parasite – evolves relatively easily, with mutations that affect the drug’s mechanism of action and which move through the population. The hope is that this dataset of drug resistance markers could provide an ‘early warning system’ – to predict drug resistance in the field and to identify a more effective drug combination.

Source

Artemisinin Partial Resistance in Ugandan Children With Complicated Malaria (JAMA)

Systematic in vitro evolution in Plasmodium falciparum reveals key determinants of drug resistance (Science)

About The Podcast

The Johns Hopkins Malaria Minute podcast is produced by the Johns Hopkins Malaria Research Institute to highlight impactful malaria research and to share it with the global community.