One Dose of Staphylococcus aureus 4C-Staph Vaccine Formulated with a Novel TLR7-Dependent Adjuvant Rapidly Protects Mice through Antibodies, Effector CD4<superscript>+</superscript> T Cells, and IL-17A.
In: PLoS ONE, Jg. 11 (2016-01-26), Heft 1, S. 1-18
Online
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Zugriff:
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]
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Titel: |
One Dose of Staphylococcus aureus 4C-Staph Vaccine Formulated with a Novel TLR7-Dependent Adjuvant Rapidly Protects Mice through Antibodies, Effector CD4<superscript>+</superscript> T Cells, and IL-17A.
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Autor/in / Beteiligte Person: | 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 |
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Zeitschrift: | PLoS ONE, Jg. 11 (2016-01-26), Heft 1, S. 1-18 |
Veröffentlichung: | 2016 |
Medientyp: | academicJournal |
ISSN: | 1932-6203 (print) |
DOI: | 10.1371/journal.pone.0147767 |
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