16 October 2019

Engineering a single-chain antibody against Trypanosoma cruzi metacyclic trypomastigotes to block cell invasion.

DOI : 10.1371/journal.pone.0223773

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Cristian Cortez, PhD.

Trypanosoma cruzi is a flagellate protozoan pathogen that causes Chagas disease.

Currently there is no preventive treatment and the efficiency of the two drugs

available is limited to the acute phase. Therefore, there is an unmet need for

innovative tools to block transmission in endemic areas. In this study, we

engineered a novel recombinant molecule able to adhere to the T. cruzi surface,

termed scFv-10D8, that consists of a single-chain variable fragment (scFv)

derived from mAb-10D8 that targets gp35/50. The synthetic gene encoding

scFv-10D8 was cloned and fused to a 6×His tag and expressed in a prokaryotic

expression system. Total periplasmic or 6xHis tag affinity-purified fractions of

scFv-10D8 retained the capacity to bind to gp35/50, as shown by Western blot

analyses. Pre-incubation of metacyclic trypomastigotes with scFv-10D8 showed a

remarkable reduction in cell invasion capacity. Our results suggest that

scFv-10D8 can be used in a paratransgenic approach to target parasites in insect

vectors, avoiding dissemination of infective forms. Such advances in the

development of this functional molecule will surely prompt the improvement of

alternative strategies to control Chagas disease by targeting mammalian host

stages.

Participating Center Researchers

Host-Pathogen Interactions Laboratory

PhD in Sciences, mention Microbiology, Inmunology, and Parasitology, Universidade Federal de São Paulo, Brasil.


LEER MÁS
Edificio2

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