Research, published in the New England Journal of Medicine, opens up new perspectives (to be confirmed) for prophylaxis against infection
A new monoclonal antibody that could prevent malaria for up to nine months in people exposed to the infection was discovered and developed at the NIH in Bethesda, Maryland (USA). The still small clinical trial was conducted by the Vaccine Research Center (VRC) of the US National Institute of Allergies and Infectious Diseases (NIAID), and funded by NIAID itself. The findings were published in the New England Journal of Medicine. Malaria continues to be a major cause of disease and death in many regions of the world, especially in infants and young people; therefore, new tools are needed to prevent this deadly disease, commented NIAID director Anthony Fauci. The reported results suggest that a single infusion of the monoclonal antibody can protect people from malaria for at least 9 months. However, more research is needed to confirm and extend this preliminary finding.
The illness
According to the World Health Organization (WHO), 229 million cases of malaria occurred worldwide in 2019, and an estimated 409,000 deaths, mostly children in sub-Saharan Africa. Malaria caused by parasites of the genus Plasmodium, which are transmitted through the bite of an infected Anopheles mosquito. Infected anopheles inject parasites (sporozoites) into the skin and from there into the bloodstream. The sporozoites travel to the liver, where they mature and multiply. Then mature plasmodium spreads throughout the body through the bloodstream and causes disease. P. falciparum is the Plasmodium species most likely to cause the most severe form of malaria, termed malignant, which, if not treated promptly, can lead to death.
Antibodies
Laboratory and animal studies have shown that antibodies can prevent malaria by neutralizing P. falciparum sporozoites in the skin and blood before they can infect liver cells. The NIAID study investigated whether the neutralizing monoclonal antibody called CIS43LS can safely provide a high level of protection from malaria in adults following careful, voluntary, and laboratory exposure to infected mosquitoes in the United States. CIS43LS is derived from a natural neutralizing antibody called CIS43. Researchers led by Robert A. Seder, head of the Cellular Immunology Section of the VRC, isolated CIS43 from the blood of a volunteer who had received an experimental malaria vaccine. Scientists found that CIS43 binds to a unique site on a parasite surface protein that is important for facilitating malaria infection and the same on all P. falciparum sporozoite variants worldwide. The researchers subsequently modified this antibody to prolong its stay in the bloodstream, resulting in CIS43LS. After animal studies for malaria prevention with CIS43LS yielded promising results, the VRC researchers initiated a Phase 1 clinical trial with CIS43LS antibody on 40 healthy adults aged 18 to 50 who were not never had malaria or had been vaccinated against the disease. The study was led by Martin Gaudinski, medical director of the VRC Clinical Studies Program, and was conducted at the NIH Clinical Center in Bethesda and the Walter Reed Army Research Institute (WRAIR) in Silver Spring, Maryland. .
I study
During the first half of the study, researchers administered a single dose of CIS43LS to 21 participants by intravenous infusion or subcutaneous injection. The researchers followed the participants for 6 months to check that intravenous infusions and subcutaneous injections of the various doses of the experimental antibody were safe and well tolerated, and titrated the presence of CIS43LS in the blood to determine their duration over time. In the second half of the study 6 people who had received an intravenous infusion during the first half of the study continued to participate, 4 of them received a second antibody infusion. Additionally, 4 new participants joined the trial by receiving a single intravenous infusion of CIS43LS. Another 7 people joined the study as controls (ie they did not receive the antibody). All participants in the second half of the study gave their informed consent to be exposed to malarial infestation as part of what is known as controlled human malaria infection (CHMI). In this procedure, volunteers are exposed to P. falciparum through infected mosquito bites in a carefully controlled environment, then they are closely monitored by medical personnel for several weeks and promptly treated if they develop malaria. CHMI has been used for decades to obtain information on the safety and protective effect of vaccine candidates and potential antimalarial drugs. Nine participants who received CIS43LS and 6 who served as controls voluntarily underwent CHMI and were closely monitored for 21 days. During that time, none of them developed malaria, while 5 of the 6 controls contracted it and therefore received standard therapy against the infection. Of the 9 participants who received CIS43LS and were protected, 7 underwent CHMI approximately 4 weeks after the infusion. The other 2 who had received a single infusion during the first half of the study contracted malaria approximately nine months later. These results indicate that a single dose of the investigational antibody can prevent malaria 1 to 9 months after infusion. To confirm this finding, a larger Phase 2 clinical trial is underway in Mali to evaluate the safety and efficacy of CIS43LS in preventing malaria infection in adults during a six-month malarial season. Results are expected in early 2022. In addition, VRC scientists are conducting further research on CIS43LS in the United States to determine the lowest dose capable of protecting people from malaria infestation. Monoclonal antibodies may represent a novel approach to preventing malaria in travelers, military personnel and healthcare workers traveling to malaria-endemic regions, ”says VRC’s Robert Seder. Further research will determine whether the antibodies can also be used for seasonal control of malaria in Africa and ultimately for disease eradication campaigns.
August 17, 2021 (change August 17, 2021 | 10:20)
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