(T0930-01-05) Targeting SA-85 Trans-Sialidase with VLP-Based Peptides: A Promising Immunologic Strategy Against Chagas Disease

Purpose: Chagas disease, caused by Trypanosoma cruzi, is one of the most prevalent neglected tropical diseases, with increasing incidence beyond endemic areas, including the United States and Europe. Current treatments have limited efficacy in clearing the parasite, often leading to chronic infection and serious complications. No approved vaccine exists for human use. T. cruzi cannot synthesize N-acetylneuraminic acid (sialic acid) and instead scavenges it from host glycoproteins via enzymes called trans-sialidases (TS). Among these, SA-85 is a conserved TS family member and has emerged as a promising antigenic target for vaccine development.

Methods: In this study, we applied immunoinformatics tools to predict immunogenic peptides derived from SA-85. Three novel peptides were selected, synthesized, and displayed as epitopes on Qβ bacteriophage virus-like particles (VLPs). These peptide-VLP constructs were used to immunize C57BL/6 mice to evaluate their immunogenic potential and ability to elicit protective immune responses against T. cruzi. Mice were immunized with the peptides (named TS-1, TS-2, and TS-3) through a three-dose schedule administered two weeks apart. Subsequently, serum and spleen samples were used to evaluate cell-mediated immune responses as well as humoral immunity.

Results: Anti-SA85 Immunoglobulin G (IgG) antibodies were assayed via indirect ELISA, showing a strong immune response across all peptides compared to the control group (p < 0.0001). Furthermore, cytokine profiling using spleen supernatant by sandwich ELISA showed significantly elevated IFN-γ levels, as high as 647.2 pg/mL in the TS-3 peptide group, which suggests potent Th-1-mediated T-cell activation. Additionally, the test for IL-4 showed moderate induction, further confirming a balanced Th1/Th2 immune response with these peptides

Conclusion: These results, which serve as a proof-of-concept trial for the SA-85 peptides constructs, suggest the peptides are viable candidates for further preclinical testing to develop a vaccine against Chagas disease.

References: Bern, C., & Montgomery, S. P. (2009). An estimate of the burden of Chagas disease in the United States. Clinical Infectious Diseases, 49(5), e52-e54.
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Anti-SA85 Total IgG by indirect ELISA using biotinylated SA-85 peptides and serum samples from immunised mice. One-way ANOVA comparison between Petides and PBS serum control. ** p<0.01, **** p<0.0001

Spleen supernatant IFN-y cytokine profile. TS-2 (372.2 pg/ml), TS-3(647.2 pg/ml), PBS (52.61 pg/ml). One-way ANOVA comparison between Petides and PBS serum control. **** p<0.0001

Spleen supernatant Il-4 cytokine profile.TS-2 (219.75 pg/ml), TS-3(299.5 pg/ml), PBS (0 pg/ml). One-way ANOVA comparison between Petides and PBS serum control. *** p<0.001