Immunization with the Tc85-Derived Peptide Displayed on Virus-like Particles Confers Protection against Trypanosoma cruzi Infection

Abstract

Chagas disease, caused by the Trypanosoma cruzi, remains a major global health burden with limited prophylactic options. We describe a vaccine platform that leverages a peptide epitope derived from the T. cruzi trans-sialidase group II (Tc85pep), displayed on the virus-like particle derived from the PP7 bacteriophage, to stimulate both innate and adaptive immunity. In silico analyses revealed that Tc85pep contains threonine residues predicted to undergo post-translational phosphorylation at conserved PKA and PKG sites and bind with high affinity to murine and human MHC class I and II alleles. Structural modeling and molecular docking suggested a potential interaction between Tc85pep and the TLR4/MD2 complex, supporting the hypothesis that the peptide may engage TLR4-associated signaling pathways. Functional analyses in TLR-deficient macrophages revealed that a multivalent conjugate of the peptide on the particle (PP7-Tc85pep) triggers nitric oxide production in a TLR4-dependent manner. In vivo, C57BL/6 mice immunized with PP7-Tc85pep exhibited a greater than 60% reduction in parasitemia and significant protection against cardiac inflammation and amastigote burden following a lethal T. cruzi challenge. The vaccine elicited a balanced Th1/Th2/Th17 immune response, marked by elevated detection of IL-10, IL-6, TNF-α, IFN-γ, and IL-17A, and provided tissue-level protection in the absence of chemotherapy. These findings identify PP7-Tc85pep as a potent, multifunctional epitope capable of engaging innate and adaptive immune pathways. The data support further development of Tc85pep-based epitope vaccines as a next-generation strategy for Chagas disease prevention.