Towards a peptide-based vaccine against Shigella sonnei : A subtractive reverse vaccinology based approach

Abstract

Shigella sonnei is one of the major causes of shigellosis in technically advanced countries and reports of its unprecedented increase are published from the Middle East, Latin America, and Asia. The pathogen exhibits resistance against first and second line antibiotics which highlights the need for the development of an effective broad-spectrum vaccine. A computational based approach comprising subtractive reverse vaccinology was used for the identification of potential peptide-based vaccine candidates in the proteome of S. sonnei reference strain (53G). The protocol revealed three essential, host non-homologous, highly virulent, antigenic, conserved and adhesive vaccine proteins: TolC, PhoE, and outer membrane porin protein. The cellular interactome of these proteins supports their direct and indirect involvement in biologically significant pathways, essential for pathogen survival. Epitope mapping of these candidates reveals the presence of surface exposed 9-mer B-cell-derived T-cell epitopes of an antigenic, virulent, non-allergen nature and have broad-spectrum potency. In addition, molecular docking studies demonstrated the deep binding of the epitopes in the binding groove and the stability of the complex with the most common binding allele in the human population, DRB1*0101. Future characterization of the screened epitopes in order to further investigate the immune protection efficacy in animal models is highly desirable.

Immuno-informatics driven proteome-wide investigation revealed novel peptide-based vaccine targets against emerging multiple drug resistant Providencia stuartii

“…Surfaceexposed (exo-proteome) or secreted proteins (secretome) are suitable vaccine targets due to their frequent contact with the extracellular environment [23]; [39]. In addition, they serve as virulence factors and increase the pathogen's ability to adhere, invade, survive, and proliferate within the host cells [22]; [25]. Therefore, a comparative subcellular localization was performed through three online tools; PSORTb (http://db.psort.org/) [40], CELLO (http://cello.life.nctu.edu.tw/) [41], and CELLO2GO (http://cello.life.nctu.edu.tw/cello2go/) [42].…”

“…Virulent proteins mediate severe infectious pathways in the host and could be attractive targets for vaccine design [22,23,24,25,25]; [43]. Several databases are available to predict the virulent potential of a protein.…”

“…The availability of genomic information allows the identification of suitable vaccine proteins in silico without the need to cultivate the pathogen. A proteome based approach for screening virulent antigens, Reverse Vaccinology (RV), has received more attention in recent years and has been used for the identification of vaccine proteins against different pathogens [21,22,23,24,25]. The RV approach was first applied to the bacterial pathogen Meningococcus B (MenB) [26], where RV played a significant role in screening for an antigen with the broadest bactericidal activity and ultimately resolved the long journey of MenB vaccine development [25]; [27].…”

“…A proteome based approach for screening virulent antigens, Reverse Vaccinology (RV), has received more attention in recent years and has been used for the identification of vaccine proteins against different pathogens [21,22,23,24,25]. The RV approach was first applied to the bacterial pathogen Meningococcus B (MenB) [26], where RV played a significant role in screening for an antigen with the broadest bactericidal activity and ultimately resolved the long journey of MenB vaccine development [25]; [27]. RV has also been applied to many other bacterial pathogens, including group A Streptococcus [28], antibiotic-resistant Staphylococcus aureus [27], Streptococcus pneumonia [27], and Chlamydia [27]; [29].…”

“…Protein-protein interactions were explored for their cellular interacting network to understand the impact of protein inhibition on overall survival of the pathogen. In the epitope mapping phase, B-cell derived T-cell peptides for the proteins were predicted [22,23,24,25] and docked into the binding cavity of DRB1*0101 allele to identify their binding mode and interactions [25].…”