title: Synthesis and immunogenicity evaluation of Salmonella enterica serovar Paratyphi A O-specific polysaccharide conjugated to diphtheria toxoid.
abstract: Salmonella enterica serovar Paratyphi A (S. Paratyphi A) is a human restricted pathogen that can cause systemic infection (paratyphoid fever) with recently increased incidence particularly in developing countries. Currently there is no licensed vaccine for prevention of infection from S. Paratyphi A. In this study the O-specific polysaccharide (OSP) of S. Paratyphi A was conjugated to diphtheria toxoid (DT) with and without adipic acid dihydrazide (ADH) as a linker. Binding of the OSP to a carrier protein was intended to convert a T-cell independent OSP response to a T-cell dependent response inducing higher levels of anti-OSP antibodies and immunological memory. These conjugates (OSP-AH-DT and OSP-DT) were evaluated for their immunogenicity in mice. The S. Paratyphi A OSP-DT conjugate induced a poor anti-OSP response less than that observed with LPS while the OSP-AH-DT conjugate induced a significantly higher antibody titer compared with LPS alone. The study also demonstrated diphtheria toxoid as a potential carrier protein for conjugate vaccine candidates using S. Paratyphi A OSP.
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.affiliation: Laboratory Science Division; International Vaccine Institute; Seoul, Republic of Korea.
authors.forename: So J
authors.initials: SJ
authors.lastname: An
authors.affiliation: Laboratory Science Division; International Vaccine Institute; Seoul, Republic of Korea.
authors.forename: Changfa
authors.initials: C
authors.lastname: Cui
authors.affiliation: Health Biotechnology Division; National Institute for Biotechnology and Genetic Engineering (NIBGE); Faisalabad, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Haque
authors.affiliation: Laboratory Science Division; International Vaccine Institute; Seoul, Republic of Korea.
authors.forename: Rodney
authors.initials: R
authors.lastname: Carbis
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D004168:Diphtheria Toxoid / Q000008:administration & dosage; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D008813:Mice, Inbred ICR; D019081:O Antigens / Q000276:immunology*; D010284:Paratyphoid Fever / Q000517:prevention & control*; D012482:Salmonella paratyphi A / Q000276:immunology*; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D004337:Drug Carriers; D019081:O Antigens; C062656:O-specific polysaccharide, Salmonella; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate
keywords: Paratyphoid; S.Paratyphi A; conjugate vaccine; diphtheria toxoid; polysaccharide antigen