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
| Autor: | Donatello Laera, Maria Rita Fontana, Fabio Bagnoli, Simona Tavarini, Silvia Rossi-Paccani, Giuliano Bensi, Guido Grandi, Francesca Mancini, Sylvie Bertholet, Ennio De Gregorio, Bruno Galletti, Michele Pallaoro, Sandra Nuti, Elisabetta Soldaini, Giuseppe Lofano, Chiara Sammicheli, Giovanna Tuscano, Letizia Arcidiacono, Rino Rappuoli, Elisabetta Monaci, Marta Bacconi, Antonina Torre |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetics and Molecular Biology (all) CD4-Positive T-Lymphocytes Physiology medicine.medical_treatment Staphylococcus lcsh:Medicine medicine.disease_cause Inbred C57BL Pathology and Laboratory Medicine Biochemistry White Blood Cells Mice Immunologic Animal Cells Immune Physiology Medicine and Health Sciences Public and Occupational Health Staphylococcus Aureus lcsh:Science Neutralizing Adjuvants Immunologic Animals Antibodies Bacterial Antibodies Neutralizing Cytokines Female Interleukin-17 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) Vaccines Multidisciplinary Immune System Proteins biology Effector T Cells Antibody titer Bacterial Animal Models Vaccination and Immunization Bacterial Pathogens Medical Microbiology Antibody Pathogens Cellular Types Anatomy Adjuvant Research Article Immune Cells 030106 microbiology Immunology Mouse Models Peritonitis Staphylococcal infections Research and Analysis Methods Microbiology Antibodies 03 medical and health sciences Model Organisms Signs and Symptoms Intensive care medicine Adjuvants Microbial Pathogens Blood Cells Bacteria lcsh:R Organisms Biology and Life Sciences Proteins Kidneys Cell Biology Renal System medicine.disease 030104 developmental biology Immunization biology.protein lcsh:Q Preventive Medicine |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 1, p e0147767 (2016) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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