Experimental Nanovaccine Offers Protection Against Repeat Exposures to Trypanosoma cruzi Through Activation of Polyfunctional T Cell Response

摘要: A parasitic protozoan Trypanosoma cruzi (T. cruzi) is the etiologic agent of Chagas disease. Previously, we have identified T. antigens TcG2 and TcG4 as potential vaccine candidates, cloned in eukaryotic expression vector pCDNA3.1 (referred p2/4) tested their ability to elicit protection from infection. In present study, subcloned two a nanoplasmid that optimized for delivery, antigen expression, regulatory compliance standards, evaluated nanovaccine nano2/4) prophylactic against repeat infections. For this, C57BL/6 mice were immunized with doses p2/4 or nano2/4 at 21 days interval, challenged after 2nd immunization, euthanized 10- 21-days post-infection (pi) corresponding parasite dissemination replication phase, respectively. Some re-challenged pi monitored 7 re-infection. Without help vaccine, elicited delayed sub-par T cell activation low levels effector molecules failed control tissue provided no challenge The was most effective eliciting an early production IFN-γ by CD4+T effector/effector memory (TEM) cells cytolytic perforin (PFN) granzyme B (GZB) CD4+ CD8+ TEM subsets 10 followed robust expansion TCM further increase pi. Consequently, nano2/4-immunized exhibited potent pi, burden inflammatory infiltrate necrosis barely detectable Furthermore, responded re-challenge infection high subpopulations offered even better than observed 1st comparison, non-vaccinated/infected clinical features sickness 59% mortality within conclusion, show delivery offers excellent, protective immunity