Details

Autor(en) / Beteiligte

• 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
• Tregoning, John S

Titel

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

Ist Teil von

• PloS one, 2016-01, Vol.11 (1), p.e0147767-e0147767

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2016

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.