Experimental malaria monoclonal antibody prevents infection

Child receiving treatment for malaria

A single injection of an experimental monoclonal antibody called L9LS was 77% effective at preventing malaria infection in children in Mali, according to the results of a mid-stage clinical trial.

L9LS binds to and neutralises ‘sporozoites’, the form of the malaria parasite transmitted by mosquitoes that invades the liver to initiate infection. It was developed by scientists at the National Institutes of Health (NIH).

“A long-acting monoclonal antibody delivered at a single health care visit that rapidly provides high-level protection against malaria in these vulnerable populations would fulfil an unmet public health need,” said Dr Jeanne Marrazzo, Director of the National Institute of Allergy and Infectious Diseases, part of NIH.

The clinical trial assessed two dose levels, with 19% of the 300mg-dose group and 28% of the 150mg-dose group developing symptomatic malaria, providing protective efficacy of 77% and 67% against symptomatic malaria, respectively.

Among children who received placebo, 81% became infected with Plasmodium falciparum, and 59% had symptomatic malaria during the six-month study period.

The authors note that the trial demonstrated for the first time that a single dose of a monoclonal antibody given by subcutaneous injection can provide high-level protection against malaria in children in an area of intense malaria transmission.

Prolonged durability in the bloodstream

In 2022, the P. falciparum parasite caused a majority of the nearly 250 million estimated cases of malaria globally and most of the more than 600,000 malaria deaths, according to the World Health Organization.

In 2020, scientists at NIAID’s Vaccine Research Center reported that they had isolated the antibody from a volunteer who had been vaccinated with an experimental malaria vaccine.

The antibody was modified with a mutation that prolonged its durability in the bloodstream following administration. In an earlier study, conducted in Mali by the same research group, a previously discovered antibody was highly protective against P. falciparum infection in adults when given intravenously. However, the new antibody was shown to be more potent in animal studies and was manufactured at a higher concentration than CIS43LS, allowing it to be given by subcutaneous injection.

The researchers are continuing clinical development of the experimental antibody, focusing on other high-risk populations, such as infants and young children, children hospitalised with severe anaemia, and pregnant women.

An ongoing clinical trial in Kenya is assessing the efficacy of the antibody in children five months to five years of age over a 12-month study period, and scientists are also conducting a clinical trial in Mali to assess the antibody in women of childbearing potential to prepare to test the antibody in pregnancy.

Diana Spencer, Senior Digital Content Editor, DDW

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