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

Abstract

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. Band 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 Band 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.

In Silico Prediction of a Multitope Vaccine against Moraxella catarrhalis: Reverse Vaccinology and Immunoinformatics

“…Only two proteins (lipopolysaccharide assembly protein LptD and outer membrane protein assembly factor BamA) out of 1615 (the number of all proteins of M. catarrhalis BBH15) were found to be essential, outer membrane localized, virulent, antigenic and non-human homologs, with appropriate molecular weight and an accepted number of transmembrane helices (fewer than two) and, therefore, they were selected to be our vaccine candidates. The same approach has been applied successfully to nominate vaccine candidates in bacterial models such as Staphylococcus aureus [ 34 ] and Shigella flexneri [ 35 ].…”

Identification and evaluation of novel vaccine candidates against Shigella flexneri through reverse vaccinology approach

“…b Antibodies raised against recombinant proteins as determined by whole-cell ELISA (Maggiore et al 2016). In a recent study of Leow et al in 2020, outer membrane proteins of S. flexneri by reverse vaccinology method were evaluated and 5 OM proteins as new vaccine candidates were identified and characterized (Leow et al 2020). In comparison to our work, they only evaluated OM proteins, and the EC proteins that are as important as OM proteins were ignored and not selected in their studies.…”

Recent Progress in Shigella and Burkholderia pseudomallei Vaccines

“…Another research group analyzed S. flexneri 2a OMPs and identified five proteins (FepA, OmpC, TolC, NlpD_1, and NlpD_2) with high antigenicity scores that are conserved among other Shigella serotypes and do not share homology with human proteins [78]. They also predicted the B and T cell epitopes of each protein but did not demonstrate immunogenicity in mice.…”