title: Immunogenicity of a Bivalent Adjuvanted Glycoconjugate Vaccine againstSalmonellaTyphimurium andSalmonellaEnteritidis.
abstract: Salmonella entericaserovars Typhimurium and Enteritidis are the predominant causes of invasive non-typhoidalSalmonella(iNTS) disease. Considering the co-endemicity ofS. Typhimurium andS. Enteritidis, a bivalent vaccine formulation against both pathogens is necessary for protection against iNTS disease, thus investigation of glycoconjugate combination is required. In the present work, we investigated the immune responses induced byS. Typhimurium andS. Enteritidis monovalent and bivalent glycoconjugate vaccines adjuvanted with aluminum hydroxide (alum) only or in combination with cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG). Humoral and cellular, systemic and local, immune responses were characterized in two different mouse strains. All conjugate vaccines elicited high levels of serum IgG against the respective O-antigens (OAg) with bactericidal activity. The bivalent conjugate vaccine induced systemic production of antibodies against bothS. Typhimurium andS. Enteritidis OAg. The presence of alum or alum + CpG adjuvants in vaccine formulations significantly increased the serum antigen-specific antibody production. The alum + CpG bivalent vaccine formulation triggered the highest systemic anti-OAg antibodies and also a significant increase of anti-OAg IgG in intestinal washes and fecal samples, with a positive correlation with serum levels. These data demonstrate the ability of monovalent and bivalent conjugate vaccines againstS. Typhimurium andS. Enteritidis to induce systemic and local immune responses in different mouse strains, and highlight the suitability of a bivalent glycoconjugate formulation, especially when adjuvanted with alum + CpG, as a promising candidate vaccine against iNTS disease.
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biotecnologie Mediche, Università di Siena , Siena , Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fiorino
authors.affiliation: GSK Vaccines Institute for Global Health S.r.l. (formerly Novartis Vaccines Institute for Global Health S.r.l.) , Siena , Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Rondini
authors.affiliation: GSK Vaccines Institute for Global Health S.r.l. (formerly Novartis Vaccines Institute for Global Health S.r.l.) , Siena , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Micoli
authors.affiliation: GSK Vaccines Institute for Global Health S.r.l. (formerly Novartis Vaccines Institute for Global Health S.r.l.) , Siena , Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Lanzilao
authors.affiliation: GSK Vaccines Institute for Global Health S.r.l. (formerly Novartis Vaccines Institute for Global Health S.r.l.) , Siena , Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Alfini
authors.affiliation: GSK Vaccines Institute for Global Health S.r.l. (formerly Novartis Vaccines Institute for Global Health S.r.l.) , Siena , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.affiliation: Jenner Institute, Nuffield Department of Medicine, University of Oxford , Oxford , UK.
authors.forename: Calman A
authors.initials: CA
authors.lastname: MacLennan
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biotecnologie Mediche, Università di Siena , Siena , Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Medaglini
keywords: O-antigen; Salmonella Enteritidis; Salmonella Typhimurium; adjuvants; bivalent vaccine; glycoconjugate vaccines; immunogenicity