New antibodies could help win the fight against malaria

Researchers have found a new class of antibodies to treat malaria, paving the way for new malarial prevention strategies. The discovery comes at a time when malaria is still a significant global health threat. 

Malaria is one of the most prevalent infectious diseases globally, particularly in lower- and middle-income countries. 

There were an estimated 263 million cases reported by the World Health Organization in 2023, up from about 248 million cases in 2022.

The study, published in Science, highlights the promise of these new antibodies in the fight against malaria. However, more clinical testing is needed before they could become available as the initial tests were performed in mouse models.

"The discovery of a new target on the sporozoite surface [the life stage of the malaria-causing parasite] represents a great breakthrough that could help development of a new next-generation antimalarial interventions," Cristina Donini told DW. 

Donini is Executive Vice President and Head of Research at Swiss not-for-profit Medicines for Malaria Venture. Donini was not part of the study.

New malaria treatments needed

New interventions have been developed against malaria, including two WHO-recommended vaccines being rolled out for children in regions where the disease is prevalent.

"While these vaccines are a big step forward in the fight against malaria, the consensus in the field is that additional tools are still urgently needed to reduce malaria burden," said study author Joshua Tan, an immunologist at National Institute of Allergy and Infectious Diseases in Maryland, US. 

Anti-malarial monoclonal antibodies (mAbs) are another promising new tool that have been shown to be safe and efficacious against infection with Plasmodium falciparum, which is the deadliest malaria-causing parasite, in adults and children in early clinical trials.

Anti-malarial antibodies work by binding to the sporozoite parasite transmitted from mosquitoes to people. They help the immune system destroy the parasite immediately, so are given when someone already has malaria. 

Vaccines work differently, training the immune system to battle future infections. 

However, current vaccines are "less than 50% protective in areas which have very high levels of malaria," Donini said. 

One problem is that current anti-malarial antibodies can interfere with malaria vaccines, reducing vaccine effectiveness even further.

"In other words, the presence of a monoclonal antibody might hinder immune responses leading to a reduced or failed vaccine efficacy," said Donini.

New anti-malarial antibody looks promising

Tan and his collaborators aimed to develop new antibodies to treat malaria which do not interfere with vaccines, by searching for new regions on the sporozoite where antibodies can bind.

One antibody, named MAD21-101, was the most potent, providing protection against malaria infection in mice.

As this antibody did not bind to the same part of the sporozoite where vaccines work, Tan said it is unlikely to interfere with vaccine effectiveness.

Donini said the new antibodies look promising as potential medication.

"Current protective drugs have to be taken every month, whereas the antibody could be given as rarely as once per season," Donini said.  

"The antibodies confer immediate protection in one single shot, whereas vaccines require three injections and it takes three months for the immune response to build up."

However, Donini warned the antibodies have only been tested in mice, so the "jury is still out" whether they will work in humans.

"Clinical data to confirm the very promising preclinical results are needed. There are two ways forward, one is to try and develop this as a new vaccine or make the protein as a therapeutic [a monoclonal antibody]," she told DW.

Can malaria be eliminated by 2030?

In 2015, the WHO began a strategy to reduce global malaria incidence and mortality rates by at least 90% by 2030.

"Although there has been notable progress against the disease, the current trajectory of malaria elimination will not allow to achieve elimination by 2030," Donini said.

Global deaths from malaria trended down between 2000-2022, yet cases remained stable in the same period, at around 250 million cases per year.

"Challenges such as persistence and spread of drug and insecticide resistance, spread of invasive and highly adaptable mosquito species, suboptimal health systems, and climate change are hindering further progress," Donini said.

What's needed to eliminate malaria, she said, are new treatments which are easier and cheaper to deliver, especially drugs which are safe for use in pregnant women and cannot be resisted by the malaria-causing parasites.

Tan said his team are working to reduce antibody production costs, "which is critical for potential development as an intervention for use in malaria-endemic regions," he said.

Edited by: Matthew Ward Agius

Source:

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