Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor.

TitleExperimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor.
Publication TypeJournal Article
Year of Publication2006
AuthorsBaral, T. Nath, Magez S., Stijlemans B., Conrath K., Vanhollebeke B., Pays E., Muyldermans S., and De Baetselier P.
JournalNat Med
Volume12
Issue5
Pagination580-4
Date Published2006 May
Type of Articleparasites
ISSN1078-8956
KeywordsAnimals, Antibodies, Protozoan, Apolipoproteins, Humans, Immunoglobulin Heavy Chains, Immunotoxins, Lipoproteins, HDL, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Trypanocidal Agents, Trypanosoma brucei rhodesiense, Trypanosomiasis, African, Variant Surface Glycoproteins, Trypanosoma
Abstract

High systemic drug toxicity and increasing prevalence of drug resistance hampers efficient treatment of human African trypanosomiasis (HAT). Hence, development of new highly specific trypanocidal drugs is necessary. Normal human serum (NHS) contains apolipoprotein L-I (apoL-I), which lyses African trypanosomes except resistant forms such as Trypanosoma brucei rhodesiense. T. b. rhodesiense expresses the apoL-I-neutralizing serum resistance-associated (SRA) protein, endowing this parasite with the ability to infect humans and cause HAT. A truncated apoL-I (Tr-apoL-I) has been engineered by deleting its SRA-interacting domain, which makes it lytic for T. b. rhodesiense. Here, we conjugated Tr-apoL-I with a single-domain antibody (nanobody) that efficiently targets conserved cryptic epitopes of the variant surface glycoprotein (VSG) of trypanosomes to generate a new manmade type of immunotoxin with potential for trypanosomiasis therapy. Treatment with this engineered conjugate resulted in clear curative and alleviating effects on acute and chronic infections of mice with both NHS-resistant and NHS-sensitive trypanosomes.

DOI10.1038/nm1395
Alternate JournalNat. Med.
PubMed ID16604085
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