Dendrimers and Parasites
Dendrimers can serve also as antiparasitic tools. They can serve for vaccination, as well as, for specific delivery of toxic cargos. As examples, applications of dendrimers for treatment of various diseases caused by Schistosoma mansoni, Fasciola gigantic
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Dendrimers and Parasites
Dendrimeric preparations have also been studied as antiparasitic agents, either vaccines or therapeutics that would be able to cope with major health problems, such as with schistosomiasis or malaria. A promising strategy is based on the development of synthetic MAP-derived vaccines (reviewed by Tam and Niederhafner et al. [12, 19]) which enable to deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Schistosoma, a parasitic disease caused by five species of schistosome platyhelminth worms adapted to man, is present in endemic areas, which cover 74 countries in Africa, the Middle East, South America, and Southeast Asia where more than 600 million people are at risk and about 200 million are actually infected [1]. MAPs with different antigens, mainly derived from the primary sequence of Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase (SG3PDH), have been tested for more than 20 years [2, 15]. It has been shown that MAPs with distinct combinations of SG3PDH-derived peptides display different efficiency against worm burden or egg count per worm [18]. Recently, immunogenicity of S. mansoni ex vivo lung-stage larvae excretory– secretory antigens and, moreover, MAPs derived from these proteins has been demonstrated [4, 5]. Novel therapeutic strategies are also necessary against malaria, treatment of which is complicated by several factors, such as drug resistance, the fact that Plasmodium vivax and Plasmodium falciparum, as the two species, distinct phylogenetically and antigenically, are responsible for the epidemics, or the necessity to target different developmental stages of the parasite [9]. Synthetic MAP vaccines tested in animals and also humans are usually derived from P. falciparum circumsporozoite protein [3, 8, 10, 20–22]. Recently, MAP vaccines harboring conserved protective epitopes from Plasmodium antigens from the sporozoite, liver, and blood stages of the life cycle that are widely recognized by populations of divergent HLA have been tested on several mouse strains [11] with results suggesting further preand clinical testing of these new-generation vaccines. Another branched peptide has been designed for immunodiagnosis of Fasciola gigantica, an etiological agent of sheep fasciolosis, as well as for protection against ˇ J. Sebest´ ık et al., Biomedical Applications of Peptide-, Glyco- and Glycopeptide Dendrimers, and Analogous Dendrimeric Structures, DOI 10.1007/978-3-7091-1206-9 17, © Springer-Verlag Wien 2012
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this disease [7]. Several complexes of the peptide FasAc14p derived from a critical enzymatic site of cathepsin L proteinase, one of the defined antigens of F. gigantica, conjugated to sequential oligopeptide carrier Ac-[Lys-Aib-Gly] 4-OH have been studied and their capability to induce immune responses documented. Dendrimeric structures have also a potential as antiparasitic drug carriers. An interesting theoretical molecular modeling study aiming to suggest a dendrimeric prodrug optimi
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