Immunoglobulin and T Cell Receptor Repertoire Changes Induced by a Prototype Vaccine Against Chagas Disease in Naive Rhesus Macaques

Autor: Jaime Ortega Lopez

Revista: Journal of Biomedical Science

Resumen:

Background A vaccine against Trypanosoma cruzi, the agent of Chagas disease, would be an excellent additional tool for disease control. A recombinant vaccine based on Tc24 and TSA1 parasite antigens was found to be safe and immunogenic in naïve macaques.
Methods We used RNA-sequencing and performed a transcriptomic analysis of PBMC responses to vaccination of naïve macaques after each vaccine dose, to shed light on the immunogenicity of this vaccine and guide the opti‑ mization of doses and formulation. We identifed diferentially expressed genes and pathways and characterized immunoglobulin and T cell receptor repertoires.
Results RNA-sequencing analysis indicated a clear transcriptomic response of PBMCs after three vaccine doses, with the up-regulation of several immune cell activation pathways and a broad non-polarized immune profle. Analy‑ sis of the IgG repertoire showed that it had a rapid turnover with novel IgGs produced following each vaccine dose, while the TCR repertoire presented several persisting clones that were expanded after each vaccine dose.
Conclusions These data suggest that three vaccine doses may be needed for optimum immunogenicity and sup‑ port the further evaluation of the protective efcacy of this vaccine.
Keywords Trypanosoma cruzi, TCR, IgG, CDR3 domain, Immune response, RNA sequencing

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