Subcutaneous antibodies protected children from malaria with 77 percent efficacy
A clinical trial of L9LS monoclonal antibodies against Plasmodium falciparum showed that a single subcutaneous injection of 300 milligrams of the drug was 70 percent effective in preventing infection. As reported in The New England Journal of Medicine, at the same dosage, the antibody protected 77 percent of cases from developing clinically evident malaria.
Malaria, caused by Plasmodium falciparum, kills 600,000 people each year, mostly children in Africa. Despite mosquito control measures, widespread use of chemoprophylaxis and case management, little progress has been made in reducing malaria deaths in recent years. In 2021, the World Health Organization recommended the RTS,S/AS01 vaccine for use in children. However, the efficacy of four doses of the malaria vaccine was 36 percent over a four-year follow-up period in children aged 5 to 17 months. The efficacy of another WHO-approved vaccine, R21/Matrix-M, was estimated at 75 percent.
Although malaria chemoprophylaxis with monoclonal antibodies is safe and effective for children and pregnant women, it is difficult to achieve high coverage because of the regimen, which requires frequent administration. The development of chemoprophylaxis with a convenient regimen would increase the coverage of preventive interventions. One solution to this problem could be the invention of a subcutaneous form. Potentially such a drug could be L9LS, a monoclonal antibody with an extended half-life targeting the highly conserved epitope of the PfCSP compound.
A team of scientists led by Peter Crompton of the National Institutes of Health conducted clinical trials of subcutaneous administration of L9LS. The first part of the study, conducted on adult volunteers, showed sufficient drug safety. In the second part (during the six-month malaria season), the scientists included 225 children from 6 to 10 years old who were divided into three groups: some were administered 150 milligrams of the drug, others - 300 milligrams, the third - a placebo.
P. falciparum infection occurred in 36 participants (48 percent) in the 150 milligram group, 30 (40 percent) in the group taking 300 milligrams, and 61 (81 percent) in the placebo group. The efficacy of L9LS against P. falciparum infection compared to placebo was 66 percent when taken at the 150 milligram dose and 70 percent when taken at the 300 milligram dose (p < 0.001 for both comparisons). Meanwhile, efficacy against clinically evident malaria was 67 percent when administered at 150 milligrams and 77 percent when administered at 300 milligrams (p < 0.001 for both comparisons).
The scientists conclude that such chemoprophylaxis can be considered as an alternative to vaccines and other biological defense regimens against malaria. In the future, the researchers plan to study the effectiveness of L9LS in reducing malaria mortality.
Other studies show that it is rational to use both approaches - both vaccination and chemoprophylaxis. For example, researchers from four countries have found that malaria vaccination improves the results of seasonal chemoprophylaxis.