title: O:2-CRM(197) conjugates against Salmonella Paratyphi A.
abstract: Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.
authors.affiliation: Novartis Vaccines Institute for Global Health, Siena, Italy. francesca.micoli@novartis.com
authors.forename: Francesca
authors.initials: F
authors.lastname: Micoli
authors.forename: Simona
authors.initials: S
authors.lastname: Rondini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gavini
authors.forename: Luisa
authors.initials: L
authors.lastname: Lanzilao
authors.forename: Donata
authors.initials: D
authors.lastname: Medaglini
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Laura B
authors.initials: LB
authors.lastname: Martin
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use; D002240:Carbohydrate Sequence; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D019081:O Antigens / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use; D010284:Paratyphoid Fever / Q000097:blood / Q000276:immunology / Q000517:prevention & control* / Q000662:veterinary; D012482:Salmonella paratyphi A / Q000737:chemistry / Q000276:immunology*; D014436:Typhoid-Paratyphoid Vaccines / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use; D018074:Vaccines, Conjugate / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use
chemical_list: D001426:Bacterial Proteins; D019081:O Antigens; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin)