PMID- 32540517 OWN - NLM STAT- MEDLINE DCOM- 20200904 LR - 20200904 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 124 DP - 2020 Aug TI - Immunopotentiation of the engineered low-molecular-weight pilin targeting Pseudomonas aeruginosa: A combination of immunoinformatics investigation and active immunization. PG - 70-82 LID - S0161-5890(20)30350-3 [pii] LID - 10.1016/j.molimm.2020.05.009 [doi] AB - Several vaccine candidates have been introduced for immunization against Pseudomonas aeruginosa strains. Despite extensive efforts in recent decades, there is no accurate immunogenic candidate against this pathogen in the market yet. Due to the rapid increase in several drug-resistant strains, P. aeruginosa has caused various health concerns worldwide. It encodes many specific virulence features, which can be used as an appropriate vaccine candidate. The primary stage of the pathogenesis of P. aeruginosa is the expression of many dynamic adhesive molecules, such as type IV pili (T4P), which acts as a principal colonization factor. It has been confirmed that three different subtypes of T4P, including type IVa (T4aP), type IVb (T4bP) and tight adherence (Tad) pili are expressed by P. aeruginosa. The IVa fimbriae type is almost the main cause of challenges to design an effective pili based-immunotherapy method. Nevertheless, in terms of heterogeneity, variability and hidden conserved binding site of T4aP, this attitude has been remained controversial and there is no permitted human study based on IVa pilin commercially. The engineered synthetic peptide-based vaccines are highly talented to mimic the target. In this research, for the first time, some dominant immunogenic features of the Flp protein, such as both B- and T-cell-associated epitopes, presence of IgE-associated epitopes, solvent-accessible surface area were evaluated by analytical immunoinformatics methods. In addition, we designed the engineered Flp pilin as an effective immunogenic substance against several clinically important P. aeruginosa strains. Moreover, by practical active immunization approaches, the humoral and cellular immune response against the extremely conserved region of the engineered synthetic Flp (EFlp) formulated in Montanide ISA 266 compared to the control group. The results of active immunization against EFlp significantly signified that EFlp-Montanide ISA 266 (EFLP-M) strongly could induce both humoral and cellular immune responses. We concluded that Flp pilin has therapeutic potential against numerous clinically significant P. aeruginosa strains and can be served as a novel immunogen for further investigations for development of effective immunotherapy methods against P. aeruginosa as a dexterous pathogen. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Ahmadbeigi, Yasaman AU - Ahmadbeigi Y AD - Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran. FAU - Chirani, Alireza Salimi AU - Chirani AS AD - Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Soleimani, Neda AU - Soleimani N AD - Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran. Electronic address: n_soleimani@sbu.ac.ir. FAU - Mahdavi, Mehdi AU - Mahdavi M AD - Recombinant Vaccine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Immunotherapy Group, The Institute of Pharmaceutical Science (TIPS), Tehran University of Medical Science, Tehran, Iran; Departments of Immunology, Pasteur Institute of Iran, Tehran, Iran. FAU - Goudarzi, Mehdi AU - Goudarzi M AD - Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: m.goudarzi@sbmu.ac.ir. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200612 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Bacterial Proteins) RN - 0 (Epitopes, B-Lymphocyte) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Flp protein, bacteria) RN - 0 (Immunodominant Epitopes) RN - 0 (Pseudomonas Vaccines) RN - 0 (Vaccines, Synthetic) SB - IM MH - Animals MH - Bacterial Proteins/*immunology MH - Computational Biology MH - Epitopes, B-Lymphocyte/immunology MH - Epitopes, T-Lymphocyte/immunology MH - Female MH - Immunodominant Epitopes/immunology MH - Mice MH - Mice, Inbred BALB C MH - Pseudomonas Infections/prevention & control MH - Pseudomonas Vaccines/*immunology MH - Pseudomonas aeruginosa/*immunology MH - Vaccination MH - Vaccines, Synthetic/immunology OTO - NOTNLM OT - Flp pilin OT - Immunogenic OT - Immunoinformatic OT - Pseudomonas aeruginosa OT - Tight adherence (tad) pili OT - Type IVb pili COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/06/17 06:00 MHDA- 2020/09/05 06:00 CRDT- 2020/06/17 06:00 PHST- 2019/09/15 00:00 [received] PHST- 2020/04/22 00:00 [revised] PHST- 2020/05/11 00:00 [accepted] PHST- 2020/06/17 06:00 [pubmed] PHST- 2020/09/05 06:00 [medline] PHST- 2020/06/17 06:00 [entrez] AID - S0161-5890(20)30350-3 [pii] AID - 10.1016/j.molimm.2020.05.009 [doi] PST - ppublish SO - Mol Immunol. 2020 Aug;124:70-82. doi: 10.1016/j.molimm.2020.05.009. Epub 2020 Jun 12.