Exploiting Virus-like Particles (VLP)-Peptide Platforms to Target SA-85 Trans-Sialidase for Chagas Disease Immunotherapy 2238706

Abstract

Abstract Introduction Chagas disease is a potentially life-threatening illness caused by Trypanosoma cruzi. An estimated 6-7 million people are infected worldwide, and over 70 million are at risk of infection. There has been an increase in reports of Chagas disease in non-endemic regions such as Europe and the United States. There are only two approved medications for treatment, which are only effective in the acute stage with overwhelming side effects. No vaccine is approved for human use. T.cruzi lacks the ability to synthesise Sialic acid and scavenges it from its host glycoproteins via enzymes called trans-sialidases (TS). Trans-sialidase SA-85 is one of the most promising targets for vaccine development, as it is conserved across different strains and forms of the parasite Methods SSA-85-derived immunogenic peptides were predicted using immunoinformatic tools, and three peptides (TS-1, TS-2, TS-3) were synthesised and displayed on Q-Beta Bacteriophage Virus-like particles. Mice of C57BL/6 background were immunized with the peptides supplemented with AddaS03 adjuvant. Three doses of the peptides were administered two weeks apart between each immunization. Thereafter, serum samples and spleen homogenate samples were utilized to evaluate the immune response against the peptides. Results Anti-SA85 Immunoglobulin G (IgG) antibodies were assayed via indirect ELISA, showing a strong immune response with the peptides compared to the control group (p < 0.0001). Furthermore, cytokines (TNF-α, IFN-γ and Granzyme B) profile using spleen homogenates and Griess reaction showed significantly elevated levels in our peptide groups in comparison to the controls. TS-2 values for IFN-γ up to 1890pg/ml and TNF-α at 271pg/ml. This shows a Th-1 biased T-cell activation. Conclusion While these results serve as a preliminary proof of concept trial for SA-85 peptide vaccine, evidence suggests they can elicit a strong immune response and are viable candidates for further preclinical research into developing a vaccine for Chagas disease. Funding Source n/a Topic Categories Vaccines and Immunotherapy (VAC)