In silico screening of antigenic B-cell derived T-cell epitopes and designing of a multi-epitope peptide vaccine for Acinetobacter nosocomialis

Globally, antibiotic-resistant and tolerated bacterial isolates of Acinetobacter species are imposing high financial cost on health care systems and as such, molecular targets with promising immune protection could provide substantive benefits to human healthcare. Here, we performed an in silica based proteome-wide screening for antigenic B-cell derived T-cell epitopes and their following use to design a multi-epitope peptide vaccine that can effectively engage the host immune system against Acinetobacter nosocomialis SSA3 strain. Epitopes of the fimbrial biogenesis outer membrane usher FimD protein: YQQGINNYL and YRTNYTTVG were revealed appropriate for multi-epitope peptide construct designing. This protein has no homology to the host, essential to the pathogen survival and is localized at the pathogen surface. The predicted epitopes have high affinity for the highly expressed DRB*0101 allele in humans based on the lowest IC50 value in MHCPred and have an exo-membrane topology for efficient immune system recognition. The designed multi-epitope peptide vaccine is composed of the mentioned shortlisted antigenic epitopes linked to each other through a GPGPG linker, and an EAAAK linker that joined the multi-epitope peptide to the Cholera B subunit from Vibrio cholera as an adjuvant to increase vaccine construct antigenicity. The vaccine construct was docked and simulated with a transmembrane toll-like receptor (TLR4) that revealed construct stable binding with the TLR4 through the adjuvant, allowing the epitopes exposed to the host immune system essential for generating effective innate and long-lasting adaptive immunity. The designed multi-epitope peptide vaccine may prompt the development of a vaccine to control refractory and deleterious A. nosocomialis infections. (C) 2019 Elsevier Inc. All rights reserved.