Antibody shot cut malaria infections 43% in young Kenyan children, phase 2 trial

The most promising new tools against childhood malaria are not vaccines but antibodies — laboratory-made proteins injected to block infection directly. A phase 2 trial in western Kenya has now tested one of them, L9LS, in the age group that carries the heaviest burden and in the transmission setting where it is hardest to protect them. The results, published in The Lancet on 1 April 2026, are encouraging but short of a knockout [s1].

Two doses of the long-acting monoclonal antibody cut the share of young children who became infected over a year by roughly two-fifths, with no evident safety concerns [s1]. The authors' own reading is that a higher dose will probably be needed to reach high-level protection where transmission is intense [s1].

Why this trial

L9LS had already shown high efficacy in children aged 6-10 years exposed to seasonal malaria [s1]. What it had not been tested against was perennial transmission — places where the parasite circulates all year — or in younger children, who are both the most vulnerable and the hardest to shield [s1]. The trial was done in Siaya county, a high perennial-transmission part of western Kenya [s1].

The disease it targets remains one of the world's largest killers of children. WHO's latest figures count 282 million malaria cases in 2024 and an estimated 610,000 deaths, with the African Region accounting for about 95% of cases and 95% of deaths — 579,000 of them — and children under five making up around 76% of the region's malaria deaths [s2].

How it was run

The trial was double-blind, two-part, randomised and placebo-controlled [s1]. Parts 1a and 1b tested safety and tolerability using an age de-escalation and dose escalation design, enrolling 96 children between 1 October 2022 and 16 January 2024, with 72 assigned to L9LS and 24 to placebo across doses of 5, 10, 20, 30 or 40 mg/kg given under the skin [s1].

Part 2 was the efficacy stage [s1]. It enrolled 324 children aged 5-59 months between 26 January and 2 June 2023, randomising them 1:1:1 to two doses of L9LS at 10-20 mg/kg given at baseline and month six (106 children), a single dose at baseline followed by placebo at month six (108 children), or placebo at both timepoints (110 children) [s1]. Children were followed for 12 months with monthly clinic visits and blood smears, and the primary efficacy endpoint was Plasmodium falciparum infection detected on smear over that year [s1].

What it found

In the two-dose group, 70 of 106 children (66%) had at least one P. falciparum infection during the 12-month follow-up, against 91 of 110 children (83%) on placebo [s1]. That translates to a protective efficacy of 42.7% (95% confidence interval 22.5-57.7; p=0.0003) [s1].

Safety looked clean [s1]. Across all parts of the trial, grade 3 or worse treatment-related adverse events occurred after four (1%) of 384 L9LS injections and two (1%) of 338 placebo injections, and all of them resolved by the study's end [s1]. The proportion of solicited and unsolicited adverse events was similar across dose groups, and there were no serious adverse events related to the trial [s1].

The honest ceiling

A 43% reduction is a real effect, but it is well below the level at which an antibody could carry a prevention programme on its own in a place like Siaya [s1]. The investigators say as much: a higher dose of L9LS might be needed to achieve high-level efficacy against malaria in young children exposed to intense perennial transmission [s1]. That is the difference between a tool that blunts infection and one that could anchor a control strategy.

The trial, funded by the Gates Foundation, was designed partly to find the dose that works, and its age-and-dose structure was built to do exactly that [s1]. The signal it delivers is that the antibody is safe in the youngest children and active against perennial transmission — the two things that were untested — while leaving the dose question open [s1].

What to watch

Monoclonal antibodies are attractive against malaria precisely because they act immediately and can be given seasonally or before a high-risk window, unlike vaccines that take weeks to build protection. The next step implied by this trial is a higher-dose evaluation in the same demanding setting, to see whether efficacy can be pushed from useful to decisive. For now, L9LS has cleared its safety and proof-of-activity bar in under-fives — and set a marker for the dose that will have to follow.

Sources

• Safety and efficacy of the monoclonal antibody L9LS for malaria prevention in children exposed to perennial malaria transmission in Kenya: a randomised, double-blind, placebo-controlled, phase 2 trial — The Lancet, 1 April 2026
• Malaria — Fact sheet — World Health Organization