title: Four-component Staphylococcus aureus vaccine 4C-staph enhances Fcγ receptor expression in neutrophils and monocytes and mitigates S. aureus infection in neutropenic mice.
abstract: Staphylococcus aureus is a human bacterial pathogen causing a variety of diseases. The occurrence of multidrug-resistant strains of Staphylococcus aureus underlines the need for a vaccine. Defining immune correlates of protection may support the design of an effective vaccine. We used a murine Staphylococcus aureus infection model, in which bacteria were inoculated in an air pouch generated on the back of the animal. Analysis of the air-pouch content in mice immunized or not with an adjuvanted multiantigen vaccine formulation, four-component S. aureus vaccine (4C-Staph), prior to infection allowed us to measure bacteria, cytokines, and 4C-Staph-specific antibodies and to analyze host immune cells recruited to the infection site. Immunization with 4C-Staph resulted in accumulation of antigen-specific antibodies in the pouch and mitigated the infection. Neutrophils were the most abundant cells in the pouch, and they showed the upregulation of Fcγ receptor (FcγR) following immunization with 4C-Staph. Reduction of the infection was also obtained in mice immunized with 4C-Staph and depleted of neutrophils; these mice showed an increase in monocytes and macrophages. Upregulation of the FcγR and the presence of antigen-specific antibodies induced by immunization with 4C-Staph may contribute to increase bacterial opsonophagocytosis. Protection in neutropenic mice indicated that an effective vaccine could activate alternative protection mechanisms compensating for neutropenia, a condition often occurring in S. aureus-infected patients.
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Torre
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Bacconi
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sammicheli
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Galletti
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Donatello
authors.initials: D
authors.lastname: Laera
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Fontana
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: De Gregorio
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bagnoli
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuti
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bertholet
authors.affiliation: Novartis Vaccines and Diagnostics, s.r.l., a GSK Company, Siena, Italy giuliano.x.bensi@gsk.com.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D009503:Neutropenia / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D017452:Receptors, IgG; D013209:Staphylococcal Vaccines