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
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
DOI:
10.1371/journal.pone.0147767
Publication Date:
2016-01-26T18:39:23Z
AUTHORS (22)
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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