1. 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.
- Author
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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, and Bagnoli, Fabio
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STAPHYLOCOCCUS aureus ,BACTERIAL vaccines ,TOLL-like receptors ,IMMUNOGLOBULINS ,CD4 antigen ,T cells ,INTERLEUKIN-17 ,LABORATORY mice - 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. [ABSTRACT FROM AUTHOR]- Published
- 2016
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