title: Physico-chemical properties of Salmonella typhi Vi polysaccharide-diphtheria toxoid conjugate vaccines affect immunogenicity.
abstract: In this study it was demonstrated that the immunogenicity of Vi polysaccharide-diphtheria toxoid conjugates was related to the physical and chemical structure of the conjugate. Conjugates were prepared in two steps, firstly binding adipic acid dihydrazide (ADH) spacer molecules to diphtheria toxoid (DT) carrier protein then secondly binding varying amounts of this derivatized DT to a fixed amount of Vi capsular polysaccharide purified from Salmonella enterica Serovar Typhi. As the amount of DT bound to the Vi increased the size of the conjugate increased but also the degree of cross-linking increased. The immunogenicity of the conjugates was tested in mice and measured by ELISA for anti Vi and anti DT IgG responses, and the results revealed a trend that as the amount of DT bound to the Vi increased the anti Vi responses increased. This study establishes a correlation between physico-chemical characteristics of the conjugate and the magnitude of the anti Vi and anti DT responses.
authors.affiliation: Vaccine Development Section, Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: An
authors.forename: Yeon Kyung
authors.initials: YK
authors.lastname: Yoon
authors.forename: Sudeep
authors.initials: S
authors.lastname: Kothari
authors.forename: Neha
authors.initials: N
authors.lastname: Kothari
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Eugene
authors.initials: E
authors.lastname: Lee
authors.forename: Deok Ryun
authors.initials: DR
authors.lastname: Kim
authors.forename: Tai Hyun
authors.initials: TH
authors.lastname: Park
authors.forename: Greg W
authors.initials: GW
authors.lastname: Smith
authors.forename: Rodney
authors.initials: R
authors.lastname: Carbis
mesh_terms: D000272:Adipates / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000992:Antitoxins / Q000097:blood; D004168:Diphtheria Toxoid / Q000737:chemistry* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000276:immunology*; D011485:Protein Binding; D014436:Typhoid-Paratyphoid Vaccines / Q000737:chemistry* / Q000276:immunology*; D017778:Vaccines, Combined / Q000737:chemistry / Q000276:immunology; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
chemical_list: D000272:Adipates; D000907:Antibodies, Bacterial; D000992:Antitoxins; D004168:Diphtheria Toxoid; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D014436:Typhoid-Paratyphoid Vaccines; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate; C057664:Vi polysaccharide vaccine, typhoid; C054154:capsular polysaccharide, Salmonella; C010011:adipic dihydrazide