title: Preparation and evaluation of immunogenic conjugates of Salmonella enterica serovar Typhi O-specific polysaccharides with diphtheria toxoid.
abstract: Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem particularly in developing countries. The available vaccines have certain limitations regarding their efficacy, and inability to induce an immune response especially in individuals under 2 years of age. Conjugate vaccines which consist of a bacteria-specific polysaccharide chemically bound to a carrier protein overcome these problems by inducing a T-cell dependent immune response characterized by enhanced immunogenicity in all ages. In this study, O-specific polysaccharides (OSP) of S. Typhi were conjugated to diphtheria toxoid (DT) using adipic acid dihydrazide (ADH) as a linker. These conjugates (OSP-AH-DT) were then evaluated for their immunogenicity using mice as a model and showed significantly higher levels of IgG ELISA titers (P = 0.0241 and 0.0245) than lipopolysaccharides alone. Different immunization  schedules were compared and it was found that schedule-B (three injections with 4-weeks interval) induced higher immune responses than schedule-A (three injections with 2-weeks interval). We showed that diphtheria toxoid can be successfully employed as a carrier protein for conjugation with Salmonella OSP and play an important role in facilitating adequate immune response.
authors.affiliation: Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
authors.forename: Aamir
authors.initials: A
authors.lastname: Ali
authors.forename: So Jung
authors.initials: SJ
authors.lastname: An
authors.forename: Changfa
authors.initials: C
authors.lastname: Cui
authors.forename: Abdul
authors.initials: A
authors.lastname: Haque
authors.forename: Rodney
authors.initials: R
authors.lastname: Carbis
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D004168:Diphtheria Toxoid / Q000737:chemistry / Q000276:immunology*; D005260:Female; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D019081:O Antigens / Q000737:chemistry / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology*; D014435:Typhoid Fever / Q000276:immunology / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000737:chemistry / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D002352:Carrier Proteins; D004168:Diphtheria Toxoid; D007074:Immunoglobulin G; D019081:O Antigens; C062656:O-specific polysaccharide, Salmonella; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate