A rapidly acting, single dose vaccine against Staphylococcus aureus would be highly beneficial for patients scheduled for major surgeries or in intensive care units. Here we show that one immunization with a multicomponent S. aureus candidate vaccine, 4C-Staph, formulated with a novel TLR7-dependent adjuvant, T7-alum, readily protected mice from death and from bacterial dissemination, both in kidney abscess and peritonitis models, outperforming alum-formulated vaccine. This increased efficacy was paralleled by higher vaccine-specific and α-hemolysin-neutralizing antibody titers and Th1/Th17 cell responses. Antibodies played a crucial protective role, as shown by the lack of protection of 4C-Staph/T7-alum vaccine in B-cell-deficient mice and by serum transfer experiments. Depletion of effector CD4+ T cells not only reduced survival but also increased S. aureus load in kidneys of mice immunized with 4C-Staph/T7-alum. The role of IL-17A in the control of bacterial dissemination in 4C-Staph/T7-alum vaccinated mice was indicated by in vivo neutralization experiments. We conclude that single dose 4C-Staph/T7-alum vaccine promptly and efficiently protected mice against S. aureus through the combined actions of antibodies, CD4+ effector T cells, and IL-17A. These data suggest that inclusion of an adjuvant that induces not only fast antibody responses but also IL-17-producing cell-mediated effector responses could efficaciously protect patients scheduled for major surgeries or in intensive care units.

One dose of staphylococcus aureus 4C-staph vaccine formulated with a novel TLR7-dependent adjuvant rapidly protects mice through antibodies, effector CD4+ T Cells, and IL-17A / Mancini, Francesca; Monaci, Elisabetta; Lofano, Giuseppe; Torre, Antonina; Bacconi, Marta; Tavarini, Simona; Sammicheli, Chiara; Arcidiacono, Letizia; Galletti, Bruno; Laera, Donatello; Pallaoro, Michele; Tuscano, Giovanna; Fontana, Maria Rita; Bensi, Giuliano; Grandi, Guido; Rossi Paccani, Silvia; Nuti, Sandra; Rappuoli, Rino; De Gregorio, Ennio; Bagnoli, Fabio; Soldaini, Elisabetta; Bertholet, Sylvie. - In: PLOS ONE. - ISSN 1932-6203. - 11:1(2016), pp. 1-18. [10.1371/journal.pone.0147767]

One dose of staphylococcus aureus 4C-staph vaccine formulated with a novel TLR7-dependent adjuvant rapidly protects mice through antibodies, effector CD4+ T Cells, and IL-17A

Grandi, Guido;
2016-01-01

Abstract

A rapidly acting, single dose vaccine against Staphylococcus aureus would be highly beneficial for patients scheduled for major surgeries or in intensive care units. Here we show that one immunization with a multicomponent S. aureus candidate vaccine, 4C-Staph, formulated with a novel TLR7-dependent adjuvant, T7-alum, readily protected mice from death and from bacterial dissemination, both in kidney abscess and peritonitis models, outperforming alum-formulated vaccine. This increased efficacy was paralleled by higher vaccine-specific and α-hemolysin-neutralizing antibody titers and Th1/Th17 cell responses. Antibodies played a crucial protective role, as shown by the lack of protection of 4C-Staph/T7-alum vaccine in B-cell-deficient mice and by serum transfer experiments. Depletion of effector CD4+ T cells not only reduced survival but also increased S. aureus load in kidneys of mice immunized with 4C-Staph/T7-alum. The role of IL-17A in the control of bacterial dissemination in 4C-Staph/T7-alum vaccinated mice was indicated by in vivo neutralization experiments. We conclude that single dose 4C-Staph/T7-alum vaccine promptly and efficiently protected mice against S. aureus through the combined actions of antibodies, CD4+ effector T cells, and IL-17A. These data suggest that inclusion of an adjuvant that induces not only fast antibody responses but also IL-17-producing cell-mediated effector responses could efficaciously protect patients scheduled for major surgeries or in intensive care units.
2016
1
Mancini, Francesca; Monaci, Elisabetta; Lofano, Giuseppe; Torre, Antonina; Bacconi, Marta; Tavarini, Simona; Sammicheli, Chiara; Arcidiacono, Letizia; Galletti, Bruno; Laera, Donatello; Pallaoro, Michele; Tuscano, Giovanna; Fontana, Maria Rita; Bensi, Giuliano; Grandi, Guido; Rossi Paccani, Silvia; Nuti, Sandra; Rappuoli, Rino; De Gregorio, Ennio; Bagnoli, Fabio; Soldaini, Elisabetta; Bertholet, Sylvie
One dose of staphylococcus aureus 4C-staph vaccine formulated with a novel TLR7-dependent adjuvant rapidly protects mice through antibodies, effector CD4+ T Cells, and IL-17A / Mancini, Francesca; Monaci, Elisabetta; Lofano, Giuseppe; Torre, Antonina; Bacconi, Marta; Tavarini, Simona; Sammicheli, Chiara; Arcidiacono, Letizia; Galletti, Bruno; Laera, Donatello; Pallaoro, Michele; Tuscano, Giovanna; Fontana, Maria Rita; Bensi, Giuliano; Grandi, Guido; Rossi Paccani, Silvia; Nuti, Sandra; Rappuoli, Rino; De Gregorio, Ennio; Bagnoli, Fabio; Soldaini, Elisabetta; Bertholet, Sylvie. - In: PLOS ONE. - ISSN 1932-6203. - 11:1(2016), pp. 1-18. [10.1371/journal.pone.0147767]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/175782
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