Abstract
An effective vaccine to reduce malaria transmission is central to control and ultimately achieve disease eradication. Recently, we demonstrated that antibodies targeting the Plasmodium falciparum surface protein P47 (Pfs47) reduce parasite transmission to Anopheles gambiae mosquitoes. Here, Plasmodium berghei (Pb) was used as a model to assess the in vivo efficacy of a P47-targeted transmission blocking vaccine (Pbs47). Mice were immunized following a prime/boost regimen and infected with P. berghei. The effect of immunization on infectivity to mosquitoes was evaluated by direct feeding on P. 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 μg/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 μg/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.
Highlights
Malaria is an infectious disease caused by Plasmodium parasites and transmitted by the bite of infected Anopheles mosquitoes (Phillips et al, 2017)
We identified the region of the P. berghei P47 (Pbs47) that confers protection and conjugated the protective antigen to the bacteriophage AP205 virus-like particle (VLP) to enhance immunogenicity
We found that VLP conjugation of the Pbs47 antigen enhanced immunogenicity and improved the Transmission Reducing Activity (TRA) when IgG was passively transferred to infected mice
Summary
Malaria is an infectious disease caused by Plasmodium parasites and transmitted by the bite of infected Anopheles mosquitoes (Phillips et al, 2017). In 2018, the WHO estimated 228 million cases of malaria worldwide leading to 405,000 deaths, compared with 262 million cases and 839,000 malaria-related deaths in 2000 (UNICEF/WHO, 2015; World Health Organization, 2019). These figures, have stalled over the last 3 years, indicating that the global response to malaria is not enough to achieve eradication. The lack of an effective vaccine, as well as the emergence of drug-resistant parasites and insecticide-resistant mosquitoes are important threats to recent gains and highlight the need for novel strategies to control malaria transmission and eliminate the disease
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