title: Conjugation of alginate to a synthetic peptide containing T- and B-cell epitopes as an induction for protective immunity against Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is a major cause of respiratory tract infections worldwide, particularly in hospitalized patients with immunosuppressed conditions and cystic fibrosis (CF). Excessive use of antibiotics means that there is currently resistance among bacterial infections to many drugs. Vaccination is a strategy that can reduce mortality and morbidity rates in infections such as those caused by P. aeruginosa. Alginate has a critical role in such infections and affects pathogenicity of the bacterium. In this work, the bioinformatics approach was used to design and synthesis a carrier peptide (ERRANAVRDVLVNEY), derived from OMP F P. aeruginosa. This peptide contained both B- and T-cell epitopes based on prediction models. Conjugation of alginate to carrier peptide was performed and then analyzed by Fourier transform infrared spectroscopy (FTIR). Results of this study on mice showed that the conjugate elicited anti-alginate-IgG that were not detected after immunization with naive alginate. The effect of the antibodies to alginate conjugate was evaluated as highly opsonic and showed moderate to high-level killing activity against two mucoid strains. IgG1 was also dominant among IgG subclasses. Mice vaccinated with the conjugate vaccine survived lethal challenges (2 ×LD 50). Furthermore, using an acute pneumonia model of infection in mice, determined that levels of P. aeruginosa in mice were significantly reduced in the vaccinated group. Thus, tests confirmed ability of this conjugate to elicit protective and opsonophagocytic antibodies that candidate our vaccine for further studies.
authors.forename: Ali
authors.initials: A
authors.lastname: Farjaha
authors.forename: Parviz
authors.initials: P
authors.lastname: Owlia
authors.forename: Seyed Davar
authors.initials: SD
authors.lastname: Siadat
authors.forename: Seyed Fazlollah
authors.initials: SF
authors.lastname: Mousavi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shafieeardestani
mesh_terms: D000464:Alginates / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung / Q000382:microbiology; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D018272:Porins / Q000737:chemistry / Q000276:immunology*; D011552:Pseudomonas Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000276:immunology
chemical_list: D000464:Alginates; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006603:Hexuronic Acids; D007074:Immunoglobulin G; C109237:OmpF protein; D010455:Peptides; D018272:Porins; D020723:Glucuronic Acid