Last Updated: 27/05/2025
Plasmodium vivax 48/45 gametocyte protein: functional characterization and vaccine potential assessment in preclinical studies
Objectives
The main goal of this proposal is to determine the vaccine potential of rPvs48/45 for human use.
This objective will be achieved through:
- To characterize the antigenicity of rPvs48/45 to map the relevant immune and functional epitopes;
- To confirm and further characterize the immunogenicity of full-length Pvs48/45 and selected fragments in non-human primates;
- To obtain the 3D structure data of the protein(s);
- To assess Natural Abs induced in individuals exposed to P. vivax and P. falciparum in endemic areas of Colombia, Brazil and Burkina Faso;
- To test Sera and affinity-purified IgG for TB capacity in MFAs;
- To address the potential cross prime/boost effect of parasite infection on Ab response elicited by immunization and vice versa by immunogenecity study; and
- To test potential cross-reactivity of elicited Abs against P. falciparum.
Malaria Vaccine and Drug Development Center (MVDC), Colombia
Montpellier University, France
Institute of Biochemistry, Switzerland
Individuals continuously exposed to malaria infections in endemic areas develop immune responses that have been shown to reduce or block parasite transmission from patients to the mosquito vector in what is called transmission-blocking (TB) immunity. In this context, antibodies (Abs) targeting specific Plasmodium antigens expressed on gametocyte, zygote, and ookinete stages can induce this blockage, providing the bases for the development of TB vaccines. One of these antigens, P48/45 is a conserved protein expressed in all Plasmodium species, required for parasite fertilization, and currently being developed as a vaccine candidate for P. falciparum. The P. vivax orthologue, cloned and expressed in E. coli, as a ~60kDa recombinant product has been shown to be highly antigenic and immunogenic. Individuals exposed to P. vivax produce Abs to Pvs48/45 which increases in an age dependent manner, and those individuals with higher a-Pvs48/45 Ab titers also display high ex vivo TB activity. Pilot studies have shown that the rPvs48/45 protein is highly immunogenic both in mice and monkeys and Abs elicited have the capacity to ex vivo block parasite transmission to mosquitoes. Together, all these data make Pvs48/45 a very promising TB vaccine candidate.
Jul 2016 — Jun 2021
$1.64M
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