- 作者: Eric Dumonteil, Weihong Tu, Hans Desale, Kelly Goff, Preston Marx, Jaime Ortega-Lopez & Claudia Herrera
- 作者服務機構: 1.Departamento de Biotecnología y Bioingeniería, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de Mexico, México 2.Department of Tropical Medicine and Infectious Disease, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, 1440 Canal St, New Orleans, Louisiana, 70112, USA 3.Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, LA, USA
- 中文摘要:
- 英文摘要:
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 optimization of doses and formulation. We identified differentially 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 profile. Analysis 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 support the further evaluation of the protective efficacy of this vaccine. - 中文關鍵字:
- 英文關鍵字: Trypanosoma cruzi, TCR, IgG, CDR3 domain, Immune response, RNA sequencing