A Two-Component DNA-Prime/Protein-Boost Vaccination Strategy for Eliciting Long-Term,Protective T Cell Immunity against Trypanosoma cruzi

In this study,we evaluated the long-term efficacy of a two-component subunit vaccine against trypanosoma cruzi infection. c57bl/6 mice were immunized with tcg2/tcg4 vaccine delivered by a dna-prime/protein-boost (d/p) approach and challenged with t. cruzi at 120 or 180 days post-vaccination (dpv). we examined whether vaccine-primed t cell immunity was capable of rapid expansion and intercepting the infecting t. cruzi. our data showed that d/p vaccine elicited cd4+ (30-38%) and cd8+ (22-42%) t cells maintained an effector phenotype up to 180 dpv,and were capable of responding to antigenic stimulus or challenge infection by a rapid expansion (cd8>cd4) with type 1 cytokine (ifnγ+ and tfnα+) production and cytolytic t lymphocyte (ctl) activity. subsequently,challenge infection at 120 or 180 dpv,resulted in 2-3-fold lower parasite burden in vaccinated mice than was noted in unvaccinated/infected mice. co-delivery of il-12- and gmcsf-encoding expression plasmids provided no significant benefits in enhancing the anti-parasite efficacy of the vaccine-induced t cell immunity. booster immunization (bi) with recombinant tcg2/tcg4 proteins 3-months after primary vaccine enhanced the protective efficacy,evidenced by an enhanced expansion (1.2-2.8-fold increase) of parasite-specific,type 1 cd4+ and cd8+ t cells and a potent ctl response capable of providing significantly improved (3-4.5-fold) control of infecting t. cruzi. further,cd8+t cells in vaccinated/bi mice were predominantly of central memory phenotype,and capable of responding to challenge infection 4-6-months post bi by a rapid expansion to a poly-functional effector phenotype,and providing a 1.5-2.3-fold reduction in tissue parasite replication. we conclude that the tcg2/tcg4 d/p vaccine provided long-term anti-t. cruzi t cell immunity,and bi would be an effective strategy to maintain or enhance the vaccine-induced protective immunity against t. cruzi infection and chagas disease. © 2015 gupta,garg.