Monoclonal antibody offers new way to protect against malaria

By Rachel Arthur contact

- Last updated on GMT

Pic:getty/drmicrobe
Pic:getty/drmicrobe

Related tags: Malaria, Monoclonal antibodies, Monoclonal antibody

One dose of an antibody drug protected from malaria infection during the malaria season in Mali, showing up to 88% effectiveness: demonstrating for the first time that a monoclonal antibody can prevent malaria in an endemic region.

The only vaccine currently recommended by the WHO is RTS,S (Mosquirix), and although other vaccines are in development it has traditionally proved to be a difficult area. While drugs to prevent malaria are available for infants, young children and travelers, the requirement for frequent dosing can be problematic while the emergency of drug resistance may also limit their usefulness.

“Thus, there is an urgent need for new, fast-acting, infrequently dosed interventions that safely provide strong protection against malaria infection,” ​says the US National Institutes of Health, which ran the clinical trial for the new monoclonal antibody.

Targeting malaria at the early stage of development

The Institute hopes that the monoclonal antibody, CIS43LS, could offer a new solution. Phase 2 data was published in The New England Journal of Medicine​ recently and presented at the American Society of Tropical Medicine & Hygiene 2022 Annual Meeting in Seattle: finding that CIS43LS 'was protective against P. falciparum infection over a 6 month malaria season without evident safety concerns'.

There were around 241 million cases of malaria globally in 2020, according to the WHO, resulting in an estimated 627,000 deaths, mostly in children in sub-Saharan Africa. These cases included more than 11 million pregnant women in Africa, resulting in an estimated 819,000 newborns with low birthweight and thus at increased risk for illness and death.

Malaria is caused by Plasmodium​ parasites, which are transmitted by mosquitos. One of the challenges in developing the arsenal against malaria is targeting the right stage of the lifecycle of the sporozoites injected into the body.

Researchers led by Robert A. Seder, M.D. (acting chief medical officer and acting associate director of the NIAID Vaccine Research Center (VRC) and chief of the VRC’s Cellular Immunology Section) isolated a naturally occurring form of a malaria antibody from the blood of a volunteer who had received an investigational malaria vaccine, and then modified the antibody to extend the length of time it would remain in the bloodstream. 

Pre-clinical trials had already shown the potential of CIS43LS to neutralize these sporozoites in the blood before they get as far as infecting liver cells: which is where they normally mature, multiply, and spread throughout the body causing illness.

Now the Phase 2 study has shown the antibody remained effective in humans for the 24 weeks of the study – approximately the length of the malaria season.

The Phase 2 trial enrolled 369 healthy, non-pregnant adults aged 18 to 55 years in the rural communities of Kalifabougou and Torodo in Mali, where intense P. falciparum​ transmission typically occurs from July through December each year.

The first part of the trial assessed the safety of three different doses of CIS43LS — 5 milligrams per kilogram of body weight, 10 mg/kg and 40 mg/kg — administered by intravenous infusion in 18 study participants, with six participants per dose level. The study team followed these participants for 24 weeks and found the antibody infusions were safe and well-tolerated.

The second part of the trial assessed the efficacy of two different doses of CIS43LS compared to a placebo. Three hundred and thirty participants were assigned at random to receive either 10 mg/kg of the antibody, 40 mg/kg, or a placebo by intravenous infusion. The study team followed these individuals for 24 weeks, testing their blood for P. falciparum ​weekly for the first 28 days and every two weeks thereafter. Any participant who developed symptomatic malaria during the trial received standard treatment from the study team.

The investigators analyzed the efficacy of CIS43LS two ways. Based on the time to first P. falciparum​ infection over the 24-week study period, the high dose (40 mg/kg) of CIS43LS was 88.2% effective at preventing infection and the lower dose (10 mg/kg) was 75% effective. An analysis of the proportion of participants infected with P. falciparum​ at any time over the 24-week study period found the high dose was 76.7% at preventing infection and the lower dose was 54.2% effective.

NIAID sponsored and funded the trial, which was led by Peter D. Crompton, M.D., M.P.H., and Kassoum Kayentao, M.D., M.P.H., Ph.D. Dr. Crompton is chief of the Malaria Infection Biology and Immunity Section in the NIAID Laboratory of Immunogenetics, and Dr. Kayentao is a professor at the University of Sciences, Techniques and Technologies (USTTB) of Bamako, Mali.

The clinical trial can be found here​ and the New England Journal of Medicine study here​. 

“These first field results demonstrating that a monoclonal antibody safely provides high-level protection against intense malaria transmission in healthy adults pave the way for further studies to determine if such an intervention can prevent malaria infection in infants, children, and pregnant women,”​ Dr. Seder said. “We hope monoclonal antibodies will transform malaria prevention in endemic regions.”

Dr. Seder and colleagues have developed a second antimalarial monoclonal antibody, L9LS, that is much more potent than CIS43LS and therefore can be administered in a smaller dose subcutaneously rather than by intravenous infusion.

An early-phase NIAID trial of L9LS in the US found​ that the antibody was safe and prevented malaria infection for 21 days in 15 out of 17 healthy adults exposed to P. falciparum​ in a carefully controlled setting. Two larger, NIAID-sponsored Phase 2 trials assessing the safety and efficacy of L9LS in infants, children and adults are underway in Mali​ and Kenya​.

“We need to expand the arsenal of available interventions to prevent malaria infection and accelerate efforts to eliminate the disease,”​ said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “These study results [for CIS43LS] suggest that a monoclonal antibody could potentially complement other measures to protect travelers and vulnerable groups such as infants, children, and pregnant women from seasonal malaria and help eliminate malaria from defined geographical areas.”

Related topics: Bio Developments

Related news

Show more