13 September 2021: Editorial
Editorial: The First Monoclonal Antibody Vaccine to Prevent Malaria Heralds a New Era of Malaria Vaccines to the Circumsporozoite Protein (PfCSP)Dinah V. Parums
Med Sci Monit 2021; 27:e934676
ABSTRACT: Malaria affects more than 3 billion people in 95 countries, with an estimated mortality rate of 400,000 per year. The female Anopheles spp mosquito most commonly transmits malaria, and the main burden of disease is due to Plasmodium falciparum. The most abundant antigen on the sporozoite surface is the Plasmodium falciparum circumsporozoite protein (PfCSP). PfCSP is required for parasite development and attachment to host hepatocytes. The first potential protein vaccine, RTS,S/ASO1, consists of a recombinant fusion antigen based on PfCSP. Initial findings from a phase 3 trial of RTS,S/ASO1 were promising but resulted in recommendations for further evaluation in large-scale trials. R21, a circumsporozoite protein-based vaccine, combined with an adjuvant, Matrix-M (MM), was recently evaluated in a phase 2 investigational study in children between 5-17 months of age in Burkina Faso. The R21/MM candidate vaccine resulted in high titers of malaria-specific antibodies. On August 26, 2021, the findings from a phase 1 trial on a new monoclonal antibody to PfCSP, CIS43LS, showed that a single dose of the CIS43LS monoclonal antibody resulted in protection against malaria. These new findings have implications for the seasonal control of malaria in endemic regions and a possible future role in public health strategies to eliminate malaria. This Editorial aims to provide the background to developing and evaluating the new malaria vaccines that target PfCSP, including the first monoclonal antibody vaccine to malaria.
Keywords: Editorial, Plasmodium falciparum, Malaria, monoclonal antibody, vaccine
The findings from this first clinical trial of a monoclonal antibody to prevent malaria have resulted in several major advances in preventing this disease. First, the effectiveness of the CIS43LS monoclonal antibody that targets the NPN junctional region of the Plasmodium falciparum circumsporozoite protein supports the inclusion of this site as a target for future next-generation vaccines. Also, this clinical trial is the first to demonstrate the potential for passive immune prevention of malaria. A single dose of the CIS43LS monoclonal antibody resulted in protection against malaria, which has implications for the seasonal control of malaria in endemic regions and a possible role in malaria elimination public health strategies. Future developments in malaria vaccines may identify more effective monoclonal antibodies, with new dosing regimens and new application routes, with expanded use for vulnerable populations in endemic geographical areas.
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