In silico design of a vaccine candidate based on autotransporters and HSP against the causal agent of shigellosis, Shigella flexneri

Intranasal Immunization of Mice with Multiepitope Chimeric Vaccine Candidate Based on Conserved Autotransporters SigA, Pic and Sap, Confers Protection against Shigella flexneri

“…S. flexneri is one of the most important causing agents of shigellosis, and increasing bacterial antibiotic resistance prompts the development of safe and effective vaccines. Previously, we made an in silico design of a vaccine that contained an adjuvant, HSP-GroEL of S. Typhi, fused with highly immunodominant epitopes from the passenger domain of SigA, Pic, and Sap autotransporters proteins of Shigella [ 16 ]. The autotransporters that were chosen for the vaccine construction are well conserved in Shigella spp.…”

“…We had previously designed an in silico gene construction with the sequences of the HSP GroEL of S. Typhi and the highly antigenic epitopes that were selected from three passenger domains of SigA, Pic, and Sap autotransporters of S. flexneri . These sequences were linked together with different proper linkers, EAAAK, GSGSAAY, and HEYGAEALERAG, according to the in silico design of vaccine that was described in León et al [ 16 ]. The constructed gene was named multiepitope S. flexneri (MESF).…”

“…Most of the vaccine candidates evaluated against Shigella present a weak immune response [ 12 ], they and confer inadequate broad protection among the different serotypes of Shigella [ 13 , 14 ]. An approach for overcoming this current problem in Shigella vaccines is the use of conserved antigens between the different serotypes of Shigella strains, like Ipas proteins, which were used as vaccines in mouse models, or in silico analyses with the conserved proteins: SigA, Pic, and Sap [ 15 , 16 ].…”

“…Sap, is a protein that has 87% identity with the amino acid sequence of Ag43 from E. coli , a protein that is involved in mechanisms of virulence, such as adhesion, aggregation, biofilm formation, and host immune evasion [ 17 , 21 ]. Hence, the described autotransporters could be considered to be targets in the development of vaccines against Shigella and some E. coli pathogenic specie [ 16 ].…”

“…Given this information and in consideration with a S. flexneri vaccine targeted at passenger domains of SigA, Pic and Sap autotransporter proteins, we implemented an in silico vaccine that was based on analysis of a chimeric multiepitope protein designed with highest immunogenic and antigenic epitopes bound to GroEL adjuvant [ 16 ]. In this work, we demonstrate that the immunization of mice with chimeric antigens displaying selected epitopes fused to GroEL induce an immune response and high protective efficacy against S. flexneri .…”