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

Giorgio Colombo,Riccardo Villa,Riccardo Capelli,Marcella Chiari,Arnone Nithichanon,Louise J Gourlay,Claudio Peri,Ganjana Lertmemongkolchai,Marina Cretich,Daniel Yero,Paola Gagni,Martino Bolognesi,Xavier Daura,Oscar Conchillo-Solé

doi:10.3390/antib7030026

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.

Highlights

IntroductionMelioidosis is an infectious disease caused by the Gram-negative, intracellular bacteriumBurkholderia pseudomallei that resides in the soil of affected countries, predominantly in the subtropical and tropical regions of the world [1]
Melioidosis is an infectious disease caused by the Gram-negative, intracellular bacteriumBurkholderia pseudomallei that resides in the soil of affected countries, predominantly in the subtropical and tropical regions of the world [1]
Proteins that are present in B. pseudomallei but not in the avirulent B. thailandensis, predicted to be non-cytoplasmic were identified and to be able to host the highest number of HLA epitopes

Summary

Introduction

Melioidosis is an infectious disease caused by the Gram-negative, intracellular bacteriumBurkholderia pseudomallei that resides in the soil of affected countries, predominantly in the subtropical and tropical regions of the world [1]. Melioidosis is an infectious disease caused by the Gram-negative, intracellular bacterium. Melioidosis impacts heavily on affected populations, and mortality rates due to fatal septicemia have been reported to be as high as 50% and 19%, in North. Underreporting of the incidence of disease coupled to the inefficacy of antibiotic treatment has led recent research efforts in the direction of alternative therapies, namely a vaccine. In addition to vaccines that are based on live-attenuated or killed bacteria, capsule polysaccharides and several subunit components have been tested for their ability to induce immune protection in vivo [3]. Reverse vaccinology involving whole genome screening of multiple pathogen strains or species for core-genome antigens is a rapid, safer, and cost-effective alternative to conventional antigen identification based on pathogen cultivation [8]. For example, based on the presence of signature sequences (signal peptides, transmembrane domains, etc.) that indicate their cell-surface location, the presence of MHC I/II binding sequences, or based on sequence homology with known antigens

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Conclusion