Novel Vaccine Candidates against Brucella melitensis Identified through Reverse Vaccinology Approach

Abstract

Global health therapeutics is a rapidly emerging facet of postgenomics medicine. In this connection, Brucella melitensis is an intracellular bacterium that causes the zoonotic infectious disease, brucellosis. Presently, no licensed vaccines are available for human brucellosis. Here, we report the identification of potential vaccine candidates against B. melitensis using a reverse vaccinology approach. Based on a systematic screening of exoproteome and secretome of B. melitensis 16 M, we identified eight proteins as potential vaccine candidates, including LPS-assembly protein LptD, a polysaccharide export protein, a cell surface protein, heme transporter BhuA, flagellin FliC, 7-alpha-hydroxysteroid dehydrogenase, immunoglobulin-binding protein EIBE, and hemagglutinin. Among these, the roles of BhuA and hemagglutinin in the virulence of Brucella are essential to establish infection. Roles of other proteins in the virulence are yet to be studied. Prediction of protein-protein interactions revealed that these proteins can interact with other proteins involved in virulence, secretion system, metabolism, and transport. From these eight potential vaccine candidates, we predicted three surface exposed novel antigenic epitopes that can induce both B-cell and T-cell immune responses. These peptides can be used for the development of either exclusive peptide vaccines or multi-component vaccines against human brucellosis. Reverse vaccinology is an important strategy for discovery of novel global health therapeutics.

In silico Identification of Potential Peptides or Allergen Shot Candidates Against Aspergillus fumigatus

“…13,19 It has been established that T and B lymphocytes act as antigenic determinants or epitopes of antigens instead of entire antigens. T cell recognizes epitopic peptides using T cell receptor that binds to either MHC I (CD8 + T cell) or MHC II (CD4 + T cells) class molecules or both present on antigen-presenting cells.…”

“…We choose the threshold value of 0.4 to increase the accurate antigenicity and to avoid false-positive results. 19 …”

“…4 With the advancement of technology or various omics approaches, they pave the way to discover novel therapeutic or drug targets for both communicable and noncommunicable diseases that have serious impact in both developed or developing countries. 19 In this study, we used the reverse vaccinology approach that resulted in identification of potential peptides or allergen shot candidate against A. fumigatus -induced infections or allergies.…”

Immunogenicity Prediction by VaxiJen: A Ten Year Overview

“…Several chimeric DNA vaccines have been designed to encode proteins omp19, omp31 and urease [154], BP26, omp31 and TF [155], and GroEL [156]. Based on systematic screening of the exoproteome and secretome of B. melitensis, Vishnu et al [157] identified eight proteins as potential vaccine candidates, including LPS-assembly protein LptD, a polysaccharide export protein, a cell surface protein, heme transporter BhuA, flagellin FliC, 7-alpha-hydroxisteroid dehydrogenase, immunoglobulin-binding protein EIBE, and hemagglutinin. Several B-and T-cell epitopes were predicted, and also from the protein omp25 [158].…”

A sandwich immunoassay for brucellosis diagnosis based on immune magnetic beads and quantum dots

“…Brucellosis can affect humans as well as many animals [1]. The prevalence of brucellosis has been observed Abbreviations: IMB, immune magnetic beads; QDs, quantum dots; SPA, staphylococcal protein A; ROC, receiver-operating characteristic; CI, confidence interval; CDC, Center for Disease Control and Prevention; RBPT, the Rose Bengal plate test; PAT, plate agglutination test; SAT, standard tube agglutination test; CFT, complement fixation test; ELISA, enzyme-linked immunosorbent assay; S-LPS, smooth lipopolysaccharides; PCR, Polymerase Chain Reaction; MNPs, magnetic nanoparticles; OMP, outer membrane protein; MES, 2-Morpholinoethanesulfonic Acid; EDC, N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine; NHS, Nhydroxysuccinimide; TMB, 3,3 ,5,5 -Tetramethylbenzidine; BSA, albumin from bovine serum; OD, optical density; AUC, area under the ROC curve; E. coli O157:H, Escherichia coli O157:H7; LM, Listeria monocytogenes; CV, coefficient of variation; PL intensity, photoluminescence intensity.…”