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Antibodies 2018, 7(3), 26; https://doi.org/10.3390/antib7030026

BPSL1626: Reverse and Structural Vaccinology Reveal a Novel Candidate for Vaccine Design against Burkholderia pseudomallei

1
Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Via Mario Bianco 9, 20131 Milano, Italy
2
Center for Complexity and Biosystems and Dipartimento di Fisica, Università degli Studi di Milano and INFN, 20133 Milano, Italy
3
Computational Biomedicine Section, Institute of Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9 Forschungszentrum Jülich, 52425 Jülich, Germany
4
Department of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy
5
Center for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
6
Institute of Biotechnology and Biomedicine (IBB), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
7
Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain
8
Pediatric Clinical Research Center “Romeo ed Enrica Invernizzi”, Cryo Electron-Microscopy Laboratory, Università degli Studi di Milano, 20133 Milano, Italy
9
Department of Chemistry, Università di Pavia, 27100 Pavia, Italy
Present address: Frau Pharma Srl, 20864 Agrate Brianza, Italy.
*
Authors to whom correspondence should be addressed.
Received: 31 May 2018 / Revised: 16 July 2018 / Accepted: 17 July 2018 / Published: 19 July 2018
(This article belongs to the Collection Computational Antibody and Antigen Design)
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Abstract

Due to significant advances in computational biology, protein prediction, together with antigen and epitope design, have rapidly moved from conventional methods, based on experimental approaches, to in silico-based bioinformatics methods. In this context, we report a reverse vaccinology study that identified a panel of 104 candidate antigens from the Gram-negative bacterial pathogen Burkholderia pseudomallei, which is responsible for the disease melioidosis. B. pseudomallei can cause fatal sepsis in endemic populations in the tropical regions of the world and treatment with antibiotics is mostly ineffective. With the aim of identifying potential vaccine candidates, we report the experimental validation of predicted antigen and type I fimbrial subunit, BPSL1626, which we show is able to recognize and bind human antibodies from the sera of Burkholderia infected patients and to stimulate T-lymphocytes in vitro. The prerequisite for a melioidosis vaccine, in fact, is that both antibody- and cell-mediated immune responses must be triggered. In order to reveal potential antigenic regions of the protein that may aid immunogen re-design, we also report the crystal structure of BPSL1626 at 1.9 Å resolution on which structure-based epitope predictions were based. Overall, our data suggest that BPSL1626 and three epitope regions here-identified can represent viable candidates as potential antigenic molecules. View Full-Text
Keywords: Burkholderia; BPSL1626 antigen; melioidosis; reverse vaccinology; crystal structure; in silico epitope predictions; type I fimbrial subunit Burkholderia; BPSL1626 antigen; melioidosis; reverse vaccinology; crystal structure; in silico epitope predictions; type I fimbrial subunit
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Capelli, R.; Peri, C.; Villa, R.; Nithichanon, A.; Conchillo-Solé, O.; Yero, D.; Gagni, P.; Chiari, M.; Lertmemongkolchai, G.; Cretich, M.; Daura, X.; Bolognesi, M.; Colombo, G.; Gourlay, L.J. BPSL1626: Reverse and Structural Vaccinology Reveal a Novel Candidate for Vaccine Design against Burkholderia pseudomallei. Antibodies 2018, 7, 26.

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