title: MF59- and Al(OH)3-Adjuvanted Staphylococcus aureus (4C-Staph) Vaccines Induce Sustained Protective Humoral and Cellular Immune Responses, with a Critical Role for Effector CD4 T Cells at Low Antibody Titers.
abstract: Staphylococcus aureus (S. aureus) is an important opportunistic pathogen that may cause invasive life-threatening infections, like sepsis and pneumonia. Due to the increasing antibiotic resistance, the development of an effective vaccine against S. aureus is needed. Although a correlate of protection against staphylococcal diseases is not yet established, several findings suggest that both antibodies and CD4 T cells might contribute to optimal immunity. In this study, we show that adjuvanting a multivalent vaccine (4C-Staph) with MF59, an oil-in-water emulsion licensed in human vaccines, further potentiated antigen-specific IgG titers and CD4 T-cell responses compared to alum and conferred protection in the peritonitis model of S. aureus infection. Moreover, we showed that MF59- and alum-adjuvanted 4C-Staph vaccines induced persistent antigen-specific humoral and T-cell responses, and protected mice from infection up to 4 months after immunization. Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune compartment is involved in vaccine-induced protection. Using CD4 T cell-depleted mice or B cell-deficient mice, we demonstrated that both T and B-cell responses contributed to 4C-Staph vaccine-mediated protective immunity. However, the role of CD4 T cells seemed more evident in the presence of low-antibody responses. This study provides preclinical data further supporting the use of the adjuvanted 4C-Staph vaccines against S. aureus diseases, and provides critical insights on the correlates of protective immunity necessary to combat this pathogen.
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Monaci
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy ; Department of Biomedical Sciences, University of Padua , Padua , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy ; Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome , Rome , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lofano
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy ; Department of Biotechnology, Chemistry and Pharmacy, University of Siena , Siena , Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Bacconi
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Tavarini
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sammicheli
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Arcidiacono
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Giraldi
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Galletti
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi Paccani
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Torre
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Fontana
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: de Gregorio
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Chiarot
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuti
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bagnoli
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Soldaini
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics S.r.l. , Siena , Italy.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bertholet
keywords: Staphylococcus aureus; T cells; adjuvant; antibodies; bacterial infection; mice; vaccination