Clin Exp Vaccine Res.  2020 Jan;9(1):15-25. 10.7774/cevr.2020.9.1.15.

Reverse vaccinology approach for the identification and characterization of outer membrane proteins of Shigella flexneri as potential cellular- and antibody-dependent vaccine candidates

• Leow CY
• Kazi A
• Hisyam Ismail CMK
• Chuah C
• Lim BH
• Leow CH
• Banga Singh KK

• KMID: 2470834
• DOI: http://doi.org/10.7774/cevr.2020.9.1.15

Abstract

PURPOSE
In the developing world, bacillary dysentery is one of the most common communicable diarrheal infections. There are approximately 169 million cases of shigellosis reported worldwide. The disease is transmitted by a group of Gram-negative intracellular enterobacteria known as Shigella flexneri, S. sonnei, S. dysenteriae, and S. boydii. Conventional treatment regimens for Shigella have been less effective due to the development of resistant strains against antibiotics. Therefore, an effective vaccine for the long term control of Shigella transmission is urgently needed.
MATERIALS AND METHODS
In this study, a reverse vaccinology approach was employed to identify most conserved and immunogenic outer membrane proteins (OMPs) of S. flexneri 2a.
RESULTS
Five OMPs including fepA, ompC, nlpD_1, tolC, and nlpD_2 were identified as potential vaccine candidates. Protein-protein interactions analysis using STRING software (https://string-db.org/) revealed that five of these OMPs may potentially interact with other intracellular proteins which are involved in beta-lactam resistance pathway. B- and T-cell epitopes of the selected OMPs were predicted using BCPred as well as Propred I and Propred (http://crdd.osdd.net/raghava/propred/), respectively. Each of these OMPs contains regions which are capable to induce B- and T-cell immune responses.
CONCLUSION
Analysis acquired from this study showed that five selected OMPs have great potential for vaccine development against S. flexneri infection. The predicted immunogenic epitopes can also be used for development of peptide vaccines or multi-epitope vaccines against human shigellosis. Reverse vaccinology is a promising strategy for the discovery of potential vaccine candidates which can be used for future vaccine development against global persistent infections.

Keyword

Antigens; Bioinformatics; Bacterial outer membrane protein; Shigella flexneri; Vaccines

MeSH Terms

Anti-Bacterial Agents
beta-Lactam Resistance
Computational Biology
Dysentery, Bacillary
Enterobacteriaceae
Epitopes
Epitopes, T-Lymphocyte
Humans
Membrane Proteins*
Membranes*
Shigella flexneri*
Shigella*
T-Lymphocytes
Vaccines
Vaccines, Subunit
Anti-Bacterial Agents
Epitopes
Epitopes, T-Lymphocyte
Membrane Proteins
Vaccines
Vaccines, Subunit

Figure

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  Fig. 1 Schematic diagram of the use of reverse vaccinology approach for the prediction of vaccine candidates against Shigella flexneri 2a and other Shigella strains. OMP, outer membrane protein.

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  Fig. 2 Subcellular localization prediction of three genomes of Shigella strains selected in this study.

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  Fig. 3 Classification of 36 outer membrane proteins of Shigella flexneri 2a according to functional

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  Fig. 4 Protein-protein interaction network of five outer membrane proteins (fepA, ompC, nlpD_1 and nlpD_2, and tolC) with other neighboring proteins in Shigella flexneri 2a. Input protein: fepA (outer membrane receptor), ompC (porin), nlpD_1 (lipoprotein NlpD), nlpD_2 (lipoprotein), and tolC (outer membrane channel protein). Predicted functional partners: acrA (multidrug efflux system transporter AcrA), acrB (multidrug efflux system protein AcrB), macB (macrolide transporter ATP-binding/permease), tonB (transporter), rpoS (RNA polymerase sigma factor RpoS), macA_3 (macrolide transporter subunit MacA), fepB (iron-enterobactin transporter periplasmic binding protein), fes (enterobactin/ferric enterobactin esterase), emrK (multidrug resistance protein K), and acrD (aminoglycoside/multidrug efflux system).

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