TROPICAL MEDICINE

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Human Derived Antibody Prevents Malaria in Mice

 

In the latest World Malaria Report of the World Health Organization, there were 216 million cases of malaria worldwide in 2016 resulting in an estimated 445,000 deaths. Almost every malarial death is caused by Plasmodium falciparum, and 91% of death occurs in Africa. Children under five years of age are most affected, accounting for two-third of the total deaths. Currently, there is no highly effective, long-lasting vaccine to prevent malaria.

 

P. falciparum is a unicellular protozoan parasite of humans, and the deadliest species of Plasmodium that cause malaria in humans. It is transmitted through the bite of a female Anopheles mosquito and is responsible for roughly 50% of all malaria cases. It causes the disease’s most dangerous form called falciparum malaria. It is also associated with the development of blood cancer (Burkitt’s lymphoma) and is classified as Group 2A carcinogen.

 

The human parasite originated from the malarial parasite Laverania found in gorillas, around 10,000 years ago. Alphonse Laveran was the first to identify the parasite in 1880, and named it Oscillaria malariae. Ronald Ross discovered its transmission by mosquito in 1897. Giovanni Battista Grassi elucidated the complete transmission from a female anopheline mosquito to humans in 1898. In 1897, William H. Welch created the name Plasmodium falciparum, which ICZN formally adopted in 1954.

 

According to an article published in Nature Medicine (Volume 24: 408-416, 2018), a human antibody has been discovered that protected mice from infection with P. falciparum. The research findings now provide the basis for future testing in humans to determine if the antibody can provide short-term protection against malaria, and also may aid in vaccine design. For the study, the authors, isolated the antibody, called CIS43, from the blood of a volunteer who had received an experimental vaccine made from whole, weakened malaria parasites (PfSPZ Vaccine-Sanaria). The volunteer was later exposed to infectious malaria-carrying mosquitoes under carefully controlled conditions and did not become infected.

 

In followup experiments, in two different models of malaria infection in mice, CIS43 was highly effective at preventing malaria infection. If confirmed through additional studies in people, CIS43 could be developed as a prophylactic measure to prevent infection for several months after administration. Such a prophylactic antibody could be useful for tourists, health care workers, military personnel or others who travel to areas where malaria is common. Moreover, if the antibody prevented malaria infection for up to six months, it might be combined with antimalarial drugs and be deployed as part of mass drug administration efforts that potentially could eliminate the disease in malaria-endemic regions.

 

Detailed examination of CIS43 revealed that it works by binding to a specific portion (epitope) of a key parasite surface protein. This epitope occurs only once along the length of the surface protein. In addition, the CIS43-binding epitope is conserved across 99.8% of all known strains of P. falciparum, making it an attractive target for next-generation experimental malaria vaccines designed to elicit production of this neutralizing antibody. The authors are planning to assess the safety and protective efficacy of the newly described CIS43 antibody next year in controlled human malaria infection challenge trials.

 

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