Malaria is one of the worlds deadliest infectious diseases, causing an estimated 249 million cases and 608,000 deaths annually, with children in the regions of Africa and South Asia being most vulnerable. Approx 2,000 cases of malaria are reported in the United States each year, by travelers from malaria-risk countries. Malaria is a mosquito-borne parasitic disease transmitted through the bite of infected female mosquitoes, which introduces Plasmodium sporozoites into the bloodstream of the human host. There are five Plasmodium parasite species that cause malaria in humans, of which, the vast majority of life-threatening cases are caused by infection with Plasmodium falciparum parasites. Researchers at NIAID have developed 11 human monoclonal antibodies that bind to a unique site on the circumsporozoite protein (CSP) on Plasmodium falciparum sporozoites that is not targeted by any known monoclonal antibodies. These antibodies do not bind to recombinant forms of CSP and as such bind to a processed or post-translational form of the protein processed by the sporozoites. In vivo studies have shown several of these antibodies can substantially reduce liver parasite burden in a mouse model of malaria. These antibodies can work cooperatively with known antibodies that target the repeat region of CSP. Some of these novel antibodies have shown enhanced protection in an animal model when combined with known protective monoclonal antibodies against sporozoites, suggesting that together they may form an effective cocktail to prevent malaria.