In vivoCharacterization ofPlasmodium bergheiP47 (Pbs47) as a Malaria Transmission-Blocking Vaccine Target

An effective vaccine to reduce malaria transmission is central to control and ultimately achieve disease eradication. Recently, we demonstrated that antibodies targeting thePlasmodium falciparumsurface protein P47 (Pfs47) reduce parasite transmission toAnopheles gambiaemosquitoes. Here,Plasmodium berghei(Pb) was used as a model to assess thein vivoefficacy of a P47-targeted transmission blocking vaccine (Pbs47). Mice were immunized following a prime/boost regimen and infected withP. berghei. The effect of immunization on infectivity to mosquitoes was evaluated by direct feeding onP. berghei-infected mice. The key region in Pbs47 where antibody binding confers protection was mapped, and the immunogenicity of this protective antigen was enhanced by conjugation to a virus-like particle. Passive immunization with 100 and 50 mu g/mL of anti-Pbs47 IgG reduced oocyst density by 77 and 67%, respectively. Furthermore, affinity purified Pbs47-specific IgG significantly reduced oocyst density by 88 and 77%, respectively at doses as low as 10 and 1 mu g/mL. These studies suggest that P47 is a promising transmission blocking target and show that antibodies to the same specific region in Pfs47 and Pbs47 confer protection.