Abstract
The TatD-like DNase of Plasmodium species has previously been characterized as a conserved antigen that plays an important role in immune evasion. Here, we found that TatD-like DNase is expressed, apart from the erythrocytic stage, throughout the developmental stages of the parasite in the mosquito vector. Antibodies to the molecule significantly blocked parasites development and transition in the mosquito gut. Further, mice immunized with recombinant TatD-like DNase showed significant resistance to parasite challenge. The antigenicity of the TatD-like antigen in combination with various adjuvants, including Freund’s adjuvants, Montanide ISA 51 and 61, Alhydrogel (aluminum hydroxide), and levamisole was investigated. It was found that immunization of the recombinant TatD-like DNase in combination with Montanide ISA 51 induced strong humoral responses that showed significant protection against parasite challenge in a mouse model. The data further support that TatD-like DNase is a functionally important molecule in the whole development cycle of the malaria parasites and a candidate for malaria vaccine development.
Highlights
The TatD DNase is a conserved protein present in most prokaryotic and eukaryotic species (Chen et al, 2014)
It is known that innate immune responses mediated by macrophages, NK cells, and oxygen radicals can sufficiently inhibit parasite development (Hou et al, 2016)
We have previously reported that Plasmodium parasites exploit the TatDlike DNase protein to counteract host cellular responses in the asexual stages in human circulation, and that TatD-like DNase specific antibodies inhibit parasite proliferation in the blood (Chang et al, 2016)
Summary
The TatD DNase is a conserved protein present in most prokaryotic and eukaryotic species (Chen et al, 2014). We have recently identified a homologous protein in the Plasmodium spp., named TatD-like DNase, which was implicated as a parasite virulent factor (Chang et al, 2016). Previous studies with immunofluorescent and immunoelectron microscopy approaches revealed that the TatD-like DNase is synthesized in the cytoplasm, translocated to the parasitophorous membrane and secreted outside the infected erythrocyte (Chang et al, 2016). Infectivity of the parasites was significantly attenuated with the deletion of the gene encoding the TatD-like DNase protein. Mice immunized with the recombinant TatD-like DNase protein combined with Freund’s adjuvant showed significant resistance to parasite infection
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