Abstract
The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are expressed during transmission from man to mosquito and are leading candidates for a malaria transmission blocking vaccine. Individually they generate transmission blocking (TB) antibodies in rodent models. Whether the single protein vaccines are suitable to use in field settings will primarily depend on their potency to elicit functional antibodies. We hypothesized that a combination of both proteins will be more potent than each protein individually. Therefore we designed chimeric proteins composed of fragments of both Pfs230 and Pfs48/45 as well as single protein fragments, and expressed these in Lactoccus lactis. Both the individual Pfs230 and Pfs48/45 fragments and chimeras elicited high levels of functional antibodies in mice. Importantly, one of the chimeric proteins elicited over threefold higher transmission blocking antibody responses than the single antigens alone. Furthermore the immunogenicity of one of the chimeras could be enhanced through coupling to a virus-like particle (VLP). Altogether these data support further clinical development of these novel constructs.
Highlights
The transmission of Plasmodium falciparum from one person to another relies on the generation of male and female gametocytes in the human host that can be picked up and spread by a mosquito
To test whether a multivalent vaccine targeting Pf s48/45 and Pf s230 is immunogenic, we generated a chimeric construct containing the Pro domain of Pf s230 fused to the 6C fragment of Pf s48/45 (Figure 1A)
Pf s230 and Pf s48/45 are expressed during the P. falciparum sexual stages in humans and elicit antibodies which effectively prevent parasite multiplication in the infected mosquito [13]
Summary
The transmission of Plasmodium falciparum from one person to another relies on the generation of male and female gametocytes in the human host that can be picked up and spread by a mosquito. Several MTBV candidates have been identified by screening monoclonal antibodies generated against P. falciparum mosquito stages for TB activity [1,2,3,4]. Pf s48/45, Pf s230, and Pf s25 are currently targeted as lead candidates for an MTBV. Pf s48/45 and Pf s230 are expressed in the gametocyte as it develops from stage III through V in the human host. After being taken up by a blood-feeding mosquito, the parasite emerges from the RBC as a gamete and after a few rounds of replication motile males fertilize female gametes to form zygotes.
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