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.
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| 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.
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| Authors | Francesca Mancini, Elisabetta Monaci, Giuseppe Lofano, Antonina Torre, Marta Bacconi, Simona Tavarini, Chiara Sammicheli, Letizia Arcidiacono, Bruno Galletti, Donatello Laera, Michele Pallaoro, Giovanna Tuscano, Maria Rita Fontana, Giuliano Bensi, Guido Grandi, Silvia Rossi-Paccani, Sandra Nuti, Rino Rappuoli, Ennio De Gregorio, Fabio Bagnoli, Elisabetta Soldaini, Sylvie Bertholet |
| Journal | PloS one (PLoS One) Vol. 11 Issue 1 Pg. e0147767 ( 2016) ISSN: 1932-6203 [Electronic] United States |
| PMID | 26812180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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