Title
Generation of novel Chagas vaccines: evolving studies/work in progress
Abstract
Chagas disease, caused by persistent chronic infection with the tropical parasite Trypanosoma cruzi, remains a severe cause of morbidity and mortality in the South American poor population. There are no Chagas vaccines for human use available nor in human clinical vaccine trials. We have previously shown that T cells alone provide protection to normally susceptible BALB/c mice against lethal systemic parasite challenge. The availability of 'humanized' mice (i.e., HLA DR1/A2 dual transgenic mice) allows us to perform similar studies eliciting data more relevant to human Chagas vaccine development. The goals of our evolving studies are to: 1) identify sequences predicted to bind multiple HLA alleles within a) the highly conserved functional (enzymatically active) trans-sialidase (TS) gene family members, b) the larger subset of non-functional TS genes, and c) the total gene subset expressed during human infection, 2) verify that predicted epitopes are presented by MHC during human T. cruzi infection, 3) prepare several DNA vaccines encoding multiple class I and class II parasite epitopes, and 4) perform immunization/challenge experiments in HLA-DR1/A2 dual transgenic mice to determine whether these novel T cell-driven vaccines induce immunity protective against acute lethal challenges as well as against chronic inflammation and disease.
Year
DOI
Venue
2011
10.1145/2147805.2147904
BCB
Keywords
Field
DocType
lethal systemic parasite challenge,chagas disease,human clinical vaccine trial,chagas vaccine,human infection,a2 dual transgenic mouse,novel chagas vaccine,class ii parasite epitopes,human use,human t. cruzi infection,human chagas vaccine development,gene family,transgenic mice,work in progress,dna vaccine
Epitope,Population,Immunology,Biology,Chagas disease,Immunity,Major histocompatibility complex,Human leukocyte antigen,Virology,T cell,DNA vaccination
Conference
Citations 
PageRank 
References 
0
0.34
0
Authors
5
Name
Order
Citations
PageRank
Christopher S. Eickhoff100.34
Matthew Ardito201.35
Eric Gustafson3174.15
William Martin401.69
Daniel F. Hoft500.34