Monoclonal antibody treatment for malaria shows encouraging results

An experimental antibody treatment prevented malaria in the majority of participants in a small but important new study, providing a measure of hope in the effort to lower the burden of the disease worldwide.

Only two of 17 participants in the Phase 1 clinical trial contracted malaria after being given the monoclonal antibody treatment, known as L9LS, according to results of the trial, which were published Wednesday in the New England Journal of Medicine.

In the study, participants at the Vaccine Research Center at the National Institutes of Health were introduced to malaria between two to six weeks after receiving L9LS. The highest two intravenous doses — 20 mg/kg and 5 mg/kg of body weight — completely prevented infection; all six participants in the control group and two participants who received L9LS – one who received the lower IV dose of 1 mg/kg and one who received the subcutaneously 5 mg/kg treatment – contracted malaria.

The study reported no safety concerns associated with the L9LS treatment.

Malaria is considered one of the “big three” infectious diseases worldwide, along with tuberculosis and HIV/AIDS. There were an estimated 241 million cases of malaria in 2020, according to data from the World Health Organization.

The WHO recommended the first-ever malaria vaccine, called RTS,S, last October after widespread clinical testing showed a 40% reduction in the risk of contracting the disease and a 30% reduction in the risk of hospitalization. But experts hope that a monoclonal antibody could further drive down malaria infection rates.

Monoclonal antibodies are most often found in cancer treatments — but vaccine biologist Robert Seder believes they may be the key to unlocking the eradication of malaria, a disease that claims the life of one child under the age of 5 every minute.

Seder, an expert at the Vaccine Research Center and the lead investigator of the new study, explained that antibodies in L9LS target a protein that covers the surface of the infecting malaria parasite early in its life cycle after it’s transferred by an infected mosquito. While vaccines trigger the patient’s immune system to create many different antibodies that target the malaria parasite, Seder describes monoclonal antibody treatments as selecting the best antibody, cloning it, and injecting the potent treatment directly into the patient.

“I have the Michael Jordan of antibodies. … Your whole [basketball] team is Michael Jordans,” he said.

The new trial is the second in-human study of L9LS. It tested a lower dose than the prior work introduced intravenously — the most common method of delivering monoclonal antibodies — as well as a moderate dose delivered subcutaneously, which will be easier to administer to young children.

Seder said he is “cautiously optimistic” about the results of future clinical trials of pediatric populations in Mali and Kenya, where prior exposure to malaria might dampen how effective a vaccine is in the broader population.

Dyann Wirth, an infectious disease research and chair of the WHO’s Malaria Policy Advisory Group, said she was unsurprised the treatment worked in light of the decades of research on monoclonal antibodies, but was holding her enthusiasm in check until the completion of clinical trials in countries with a high presence of malaria.

Wirth said she was most interested in the reaction of children to the treatment — participants in this Phase 1 clinical trial were healthy adults aged 18 to 50 years — and the length of efficacy. While participants were exposed to malaria between two to six weeks after treatment, that’s a short time given some countries with high rates of malaria have rainy seasons lasting for six months, while others, like Kenya, have malaria-laden mosquitoes year-round.

An ideal future study would be large and would compare the efficacy of the vaccine, the monoclonal antibody treatment, and both together, said Richard Wu, first author on the Phase 1 clinical trial study, adding that he doesn’t expect them to negatively interact with each other. The monoclonal antibody treatment is “a tool that we want to have in this fight against this disease, but that doesn’t necessarily mean it has to be the only tool that solves everything,” Wu said.

Even if L9LS proves its mettle in larger trials, there may still be concerns about cost. Monoclonal antibody treatments are typically expensive. But Seder believes costs can be lowered to a reasonable range if the clinical trial results indicate that the treatment can save lives. He said he’s currently in discussions about licensing the antibodies to produce them at low cost.