title: In silico design of an immunogen against Acinetobacter baumannii based on a novel model for native structure of Outer membrane protein A.
abstract: Outer membrane protein A (OmpA) is the most promising vaccine candidate against one of the most successful nosocomial pathogens, A. baumannii. Despite advantages of the antigen, its cytotoxicity could be considered as a challenge in clinical trials. In order to improve this effective immunogen, rational vaccine design strategies such as structure-based vaccinology should be assessed. However, native structure of OmpA remains controversial. The present study is conducted to address the native structure of OmpA; then, a novel immunogen with lower toxicity and higher antigenicity was designed based on structural vaccinology. Various bioinformatic and immunoinformatic tools were harnessed to perform analyses such as topology, secondary structure, and tertiary structure predictions as well as B-cell epitope predictions. A novel 12-stranded model is suggested for OmpA. K320and K322were substituted by Alanine, "NADEEFWN" sequence was replaced by "YKYDFDGVNRGTRGTSEEGTL", Position 1-24 at the N-terminus and the C-terminal sequence "VVQPGQEAAAPAAAQ" were removed. The designed construct has more epitope density and antigenic properties with higher immunogenicity while its cytotoxicity is decreased. Moreover, this single cross-protective antigen could trigger antibodies rendering protection against two important nosocomial pathogens i.e. Pseudomonas aeruginosa and A. baumannii.
authors.affiliation: Department of Biology, Shahed University, Tehran, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Jahangiri
authors.affiliation: Department of Biology, Shahed University, Tehran-Qom Express Way, Tehran, Iran. Electronic address: rasooli@shahed.ac.ir.
authors.forename: Iraj
authors.initials: I
authors.lastname: Rasooli
authors.affiliation: Department of Microbiology, Shahed University Faculty of Medical Sciences, Tehran, Iran; Molecular Microbiology Research Center (MMRC), Shahed University, Tehran, Iran.
authors.forename: Parviz
authors.initials: P
authors.lastname: Owlia
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas Ali Imani
authors.initials: AA
authors.lastname: Fooladi
authors.affiliation: Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Salimian
mesh_terms: D000151:Acinetobacter Infections / Q000276:immunology / Q000517:prevention & control; D040981:Acinetobacter baumannii / Q000276:immunology*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D003198:Computer Simulation; D003428:Cross Infection / Q000276:immunology / Q000517:prevention & control; D003601:Cytotoxicity Tests, Immunologic; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D000071497:Immunogenicity, Vaccine; D008968:Molecular Conformation; D011550:Pseudomonas aeruginosa / Q000276:immunology; D020539:Sequence Analysis, Protein; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D018985:Epitopes, B-Lymphocyte; D014614:Vaccines, Synthetic; C078167:OMPA outer membrane proteins
keywords: B-cell epitopes; OmpA; P. aeruginosa; Structural vaccinology; Structure prediction; Vaccine design