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: CD4-Positive T-Lymphocytes; 0301 basic medicine; Staphylococcus aureus; Science; Mice; 03 medical and health sciences; Adjuvants, Immunologic; Animals; Adjuvants, Immunologic; Animals; Antibodies, Bacterial; Antibodies, Neutralizing; CD4-Positive T-Lymphocytes; Cytokines; Female; Interleukin-17; Mice; Mice, Inbred C57BL; Spleen; Staphylococcal Infections; Staphylococcal Vaccines; Staphylococcus aureus; Survival Rate; Th1 Cells; Th17 Cells; Toll-Like Receptor 7; Medicine (all); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all); Q; Interleukin-17; R; Staphylococcal Vaccines; Staphylococcal Infections; Th1 Cells; Antibodies, Bacterial; Antibodies, Neutralizing; 3. Good health; Mice, Inbred C57BL; Survival Rate; Toll-Like Receptor 7; Medicine; Cytokines; Th17 Cells; Female; Spleen; Research Article

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.