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

• DOI: 10.1371/journal.pone.0147767
• Publication Date: 2016-01-26T18:39:23Z
• 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
• Keywords: Alum; Pneumolysin

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