Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor.
Nat Med
; 12(5): 580-4, 2006 May.
Article
en En
| MEDLINE
| ID: mdl-16604085
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apolipoproteínas
/
Tripanocidas
/
Tripanosomiasis Africana
/
Glicoproteínas Variantes de Superficie de Trypanosoma
/
Inmunotoxinas
/
Lipoproteínas HDL
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Bélgica