Extent of polymorphism and selection pressure on the Trypanosoma cruzi vaccine candidate antigen Tc24.

Autor: Arnal A; Laboratorio de Parasitología Centro de Investigaciones Regionales 'Dr Hideyo Noguchi' Universidad Autónoma de Yucatán Mérida Mexico.; Departamento de Ecología de la Biodiversidad Instituto de Ecología Universidad Nacional Autónoma de México Ciudad de México México., Villanueva-Lizama L; Laboratorio de Parasitología Centro de Investigaciones Regionales 'Dr Hideyo Noguchi' Universidad Autónoma de Yucatán Mérida Mexico., Teh-Poot C; Laboratorio de Parasitología Centro de Investigaciones Regionales 'Dr Hideyo Noguchi' Universidad Autónoma de Yucatán Mérida Mexico., Herrera C; Department of Tropical Medicine School of Public Health and Tropical Medicine Tulane University New Orleans LA USA.; Vector-Borne and Infectious Disease Research Center Tulane University New Orleans LA USA., Dumonteil E; Department of Tropical Medicine School of Public Health and Tropical Medicine Tulane University New Orleans LA USA.; Vector-Borne and Infectious Disease Research Center Tulane University New Orleans LA USA.
Jazyk: angličtina
Zdroj: Evolutionary applications [Evol Appl] 2020 Sep 10; Vol. 13 (10), pp. 2663-2672. Date of Electronic Publication: 2020 Sep 10 (Print Publication: 2020).
DOI: 10.1111/eva.13068
Abstrakt: Introduction: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi , is a major public health problem in the Americas, and existing drugs have severe limitations. In this context, a vaccine would be an attractive alternative for disease control. One of the difficulties in developing an effective vaccine lies in the high genetic diversity of T. cruzi . In this study, we evaluated the level of sequence diversity of the leading vaccine candidate Tc24 in multiple parasite strains.
Methods and Results: We quantified its level of polymorphism within and between T. cruzi discrete typing units (DTUs) and how this potential polymorphism is structured by different selective pressures. We observed a low level of polymorphism of Tc24 protein, weakly associated with parasite DTUs, but not with the geographic origin of the strains. In particular, Tc24 was under strong purifying selection pressure and predicted CD8 + T-cell epitopes were mostly conserved. Tc24 strong conservation may be associated with structural/functional constrains to preserve EF hand domains and their calcium-binding loops, and Tc24 is likely important for the parasite fitness.
Discussion: Together, these results show that a vaccine based on Tc24 is likely to be effective against a wide diversity of parasite strains across the American continent, and further development of this vaccine candidate should be a high priority.
(© 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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