Abstract
BackgroundTransmission-blocking vaccine (TBV) is a promising strategy for malaria elimination. It is hypothesized that mixing or fusing two antigens targeting different stages of sexual development may provide higher transmission-blocking activity than these antigens used individually.MethodsA chimeric protein composed of fragments of Pbg37 and PSOP25 was designed and expressed the recombinant protein in Escherichia coli Rosetta-gami B (DE3). After immunizing mice with individual recombinant proteins Pbg37 and PSOP25, mixed proteins (Pbg37+PSOP25), or the fusion protein (Pbg37-PSOP25), the antibody titers of individual sera were analyzed by ELISA. IFA and Western blot were performed to test the reactivity of the antisera with the native proteins in the parasite. The transmission-blocking activity of the different immunization schemes was assessed using in vitro and in vivo assays.ResultsWhen Pbg37 and PSOP25 were co-administered in a mixture or as a fusion protein, they elicited similar antibody responses in mice as single antigens without causing immunological interference with each other. Antibodies against the mixed or fused antigens recognized the target proteins in the gametocyte, gamete, zygote, and ookinete stages. The mixed proteins or the fusion protein induced antibodies with significantly stronger transmission-reducing activities in vitro and in vivo than individual antigens.ConclusionsThere was no immunological interference between Pbg37 and PSOP25. The bivalent vaccines, which expand the portion of the sexual development during which the transmission-blocking antibodies act, produced significantly stronger transmission-reducing activities than single antigens. Altogether, these data provide the theoretical basis for the development of combination TBVs targeting different sexual stages.Graphical
Highlights
Transmission-blocking vaccine (TBV) is a promising strategy for malaria elimination
Antigens expressed during the sexual development of the malaria parasites, either expressed in gametocytes or gametes, are called pre-fertilization antigens, while those expressed in zygotes and ookinetes are considered post-fertilization antigens [7]
Expression of recombinant proteins To explore the immunogenicity of a bivalent vaccine targeting Pbg37 and PSOP25, we generated a chimeric construct containing the L ys26-Asn88 fragment of Pbg37 fused to the Met45-Glu245 fragment of PSOP25 using a flexible linker sequence (GGGGS)3 (Fig. 1a)
Summary
It is hypothesized that mixing or fusing two antigens targeting different stages of sexual development may provide higher transmissionblocking activity than these antigens used individually. Among the vaccine designs against malaria parasites, transmissionblocking vaccines (TBVs), which target the sexual and/ or sporogonic development of the parasite, are intended to reduce the transmission of malaria parasites from humans to mosquitoes [3]. The malaria parasite has a complex life cycle, including developmental stages in both the human host and the mosquito vector. The transmission of malaria begins with the formation of the sexual precursor stage, gametocytes, in humans. Antigens expressed during the sexual development of the malaria parasites, either expressed in gametocytes or gametes, are called pre-fertilization antigens, while those expressed in zygotes and ookinetes are considered post-fertilization antigens [7]
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