92 research outputs found
Theranostic applications of phage display to control leishmaniasis: Selection of biomarkers for serodiagnostics, vaccination, and immunotherapy
© 2015, Sociedade Brasileira de Medicina Tropical. All rights reserved. Phage display is a high-throughput subtractive proteomic technology used for the generation and screening of large peptide and antibody libraries. It is based on the selection of phage-fused surface-exposed peptides that recognize specific ligands and demonstrate desired functionality for diagnostic and therapeutic purposes. Phage display has provided unmatched tools for controlling viral, bacterial, fungal, and parasitic infections, and allowed identification of new therapeutic targets to treat cancer, metabolic diseases, and other chronic conditions. This review presents recent advancements in serodiagnostics and prevention of leishmaniasis -an important tropical parasitic disease- achieved using phage display for the identification of novel antigens with improved sensitivity and specificity. Our focus is on theranostics of visceral leishmaniasis with the aim to develop biomarker candidates exhibiting both diagnostic and therapeutic potential to fight this important, yet neglected, tropical disease.Peer Reviewe
Subtractive phage display selection from canine visceral leishmaniasis identifies novel epitopes that mimic leishmania infantum antigens with potential serodiagnosis applications
Visceral leishmaniasis (VL) is a zoonotic disease that is endemic to Brazil, where dogs are the main domestic parasite reservoirs,
and the percentages of infected dogs living in regions where canine VL (CVL) is endemic have ranged from 10% to 62%. Despite
technological advances, some problems have been reported with CVL serodiagnosis. The present study describes a sequential
subtractive selection through phage display technology from polyclonal antibodies of negative and positive sera that resulted in
the identification of potential bacteriophage-fused peptides that were highly sensitive and specific to antibodies of CVL. A negative
selection was performed in which phage clones were adhered to purified IgGs from healthy and Trypanosoma cruzi-infected
dogs to eliminate cross-reactive phages. The remaining supernatant nonadhered phages were submitted to positive selection
against IgG from the blood serum of dogs that were infected with Leishmania infantum. Phage clones that adhered to purified
IgGs from the CVL-infected serum samples were selected. Eighteen clones were identified and their reactivities tested by a phage
enzyme-linked immunosorbent assay (phage-ELISA) against the serum samples from infected dogs (n 31) compared to those
from vaccinated dogs (n 21), experimentally infected dogs with cross-reactive parasites (n 23), and healthy controls (n
17). Eight clones presented sensitivity, specificity, and positive and negative predictive values of 100%, and they showed no crossreactivity
with T. cruzi- or Ehrlichia canis-infected dogs or with dogs vaccinated with two different commercial CVL vaccines in
Brazil. Our study identified eight mimotopes of L. infantum antigens with 100% accuracy for CVL serodiagnosis. The use of
these mimotopes by phage-ELISA proved to be an excellent assay that was reproducible, simple, fast, and inexpensive, and it can
be applied in CVL-monitoring programsThis work was supported by grants from the Pró-Reitoria de Pesquisa
of UFMG (supported 03/2013), the Instituto Nacional de Ciência e
Tecnologia em Nano-Biofarmacêutica (INCT Nano-Biofar), Rede
Nanobiotec/Brasil-UFU (CAPES), PRONEX-FAPEMIG (APQ-01019-
09), FAPEMIG (APQ-00496-11 and APQ-00819-12), and CNPq (APQ-
472090/2011-9 and APQ-482976/2012-8). E.A.F.C. and L.R.G. are recipients
of grants from CNPq. M.A.C.-F. is the recipient of a grant from
FAPEMIG/CAPE
Incorporating biodiversity responses to land use change scenarios for preventing emerging zoonotic diseases in areas of unknown host-pathogen interactions
The need to reconcile food production, the safeguarding of nature, and the protection of public health is imperative in a world of continuing global change, particularly in the context of risks of emerging zoonotic disease (EZD). In this paper, we explored potential land use strategies to reduce EZD risks using a landscape approach. We focused on strategies for cases where the dynamics of pathogen transmission among species were poorly known and the ideas of “land-use induced spillover” and “landscape immunity” could be used very broadly. We first modeled three different land-use change scenarios in a region of transition between the Cerrado and the Atlantic Forest biodiversity hotspots. The land-use strategies used to build our scenarios reflected different proportions of native vegetation cover, as a proxy of habitat availability. We then evaluated the effects of the proportion of native vegetation cover on the occupancy probability of a group of mammal species and analyzed how the different land-use scenarios might affect the distribution of species in the landscape and thus the risk of EZD. We demonstrate that these approaches can help identify potential future EZD risks, and can thus be used as decision-making tools by stakeholders, with direct implications for improving both environmental and socio-economic outcomes
- …