Invasion-inhibitory peptides chosen by natural selection analysis as an antimalarial strategy.

Autor: Rodríguez-Obediente K; Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; MSc programme in Microbiology, Biotechnology Institute, Universidad Nacional de Colombia, Bogotá, Colombia., Yepes-Pérez Y; Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia., Benavides-Ortiz D; Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; School of Health Sciences, Universidad Colegio Mayor de Cundinamarca, Bogotá, Colombia., Díaz-Arévalo D; Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Animal Science Faculty, Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A), Bogotá, Colombia., Reyes C; Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia., Arévalo-Pinzón G; Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Microbiology Department, Science Faculty, Pontificia Universidad Javeriana, Bogotá, Colombia., Patarroyo MA; Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Microbiology Department, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia. Electronic address: mapatarr.fidic@gmail.com.
Jazyk: angličtina
Zdroj: Molecular immunology [Mol Immunol] 2023 Nov; Vol. 163, pp. 86-103. Date of Electronic Publication: 2023 Sep 26.
DOI: 10.1016/j.molimm.2023.09.013
Abstrakt: Plasmodium vivax's biological complexity has restricted in vitro culture development for characterising antigens involved in erythrocyte invasion and their immunological relevance. The murine model is proposed as a suitable alternative in the search for therapeutic candidates since Plasmodium yoelii uses homologous proteins for its invasion. The AMA-1 protein is essential for parasite invasion of erythrocytes as it is considered an important target for infection control. This study has focused on functional PyAMA-1 peptides involved in host-pathogen interaction; the protein is located in regions under negative selection as determined by bioinformatics analysis. It was found that pyama1 has two highly conserved regions amongst species (>70%) under negative selection. Fourteen synthetic peptides spanning both conserved regions were evaluated; 5 PyAMA-1 peptides having high specific binding (HABP) to murine erythrocytes were identified. The parasite's invasion inhibition capability was analysed through in vitro assays, suggesting that peptides 42681 (43-ENTERSIKLINPWDKYMEKY-62), 42903 (206-RYSSNDANNENQPFSFTPEK-225) and 42904 (221-FTPEKIENYKDLSYLTKNLR-240) had greater than 50% inhibition profile and restricted P. yoelii intra-erythrocyte development. This work proposes that the screening of conserved HABPs under negative selective pressure might be good candidates for developing a synthetic anti-malarial vaccine since they share functionally-relevant characteristics, such as interspecies conservation, specific RBC binding profile, invasion and parasite development inhibition capability, and the predicted B-epitopes within were recognised by sera obtained from experimentally-infected mice.
Competing Interests: Conflict of interest The authors declare that the research was carried out in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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