Staphylococcus aureus vaccine compositions

Abstract

Provided herein, inter alia, are vaccine compositions including a non-toxin Staphylococcus aureus antigen and an IL-17 activating adjuvant. The vaccine compositions are contemplated to induce a potent immune response against Staphylococcus aureus.

Description

PATENT Attorney Docket No.: 048537-662001WO Client Ref. No. SD2024-044 STAPHYLOCOCCUS AUREUS VACCINE COMPOSITIONS CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No.63,542,706, filed October 5, 2023, which is hereby incorporated by reference in its entirety and for all purposes. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (048537- 662001WO_Sequence_Listing_ST26.xml; Size 23,014 bytes; and Date of Creation: October 4, 2024) are hereby incorporated by reference in their entirety. STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

[0003] This invention was made with government support under R01 AI144694 and R01 AI127406 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND

[0004] Staphylococcus aureus (SA) is an opportunistic pathogen that causes life-threatening skin and soft tissue infections in both immunocompromised and healthy individuals. Due to SA, about 20000 deaths occur annually in the United States alone. Importantly, this pathogen has gained resistance to almost all the available antibiotics, even the last resort antibiotic, Vancomycin. Vaccination remains the best prophylactic strategy to contain pathogenic infections. To date, more than 25 vaccine clinical trials have failed against SA for unknown reasons.

[0005] Provided herein, inter alia, are solutions to these and other problems in the art. BRIEF SUMMARY

[0006] In an aspect is provided a vaccine including a non-toxin Staphylococcus aureus (SA) antigen and an IL-17 activating adjuvant.

[0007] In an aspect is provided a pharmaceutical composition including a therapeutically or prophylactically effective amount of the vaccine provided herein including embodiments thereof and a pharmaceutically acceptable excipient.

[0008] In an aspect is provided a method of treating or preventing an SA-associated disease in a subject in need of such treatment or prevention, the method including administering a therapeutically or prophylactically effective amount of the vaccine provided herein including embodiments thereof to the subject.

[0009] In an aspect is provided a method of immunizing a subject susceptible to SA infection, including administering to the subject the vaccine provided herein including embodiments thereof.

[0010] In an aspect is provided a vaccine including a Staphylococcus aureus (SA) antigen and an IL-17 activating adjuvant. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIG.s 1A-1H. Adjuvants mediate efficient protection in SA-exposed mice model. FIG.1A) Naive C57BL / 6 mice or SA-exposed (3 times at 7-D intervals) mice were i.p. vaccinated with Alum, AIsdB, CAF01 or CAF01IsdB (3 times at 7-D intervals), then 14 days post-last vaccination mice were challenged with SA (3.5x107CFU) and 20 h later tissue CFU counts (n=19-26). FIG.1B) Naive C57BL / 6 mice or SA-exposed mice were vaccinated with PBS, ß-glucan, or ß-glucanIsdB and then SA challenge and tissue CFU counts as in FIG.1A. (n=3-10). FIG.s 1C, 1D) Naive C57BL / 6 mice or SA-exposed mice were vaccinated with TDB alone or TDBIsdB (FIG.1C) and TLR7 alone or TLR7IsdB (FIG.1D), then SA challenged and tissue CFU counts as in FIG.1A (n=5-14). FIG.1E) Naive C57BL / 6 mice or SA-exposed mice were vaccinated with PBS, AS04 (Alum+MPLA) or AS04IsdB and then SA challenge and tissue CFU counts as in FIG.1A ((n=5-15). FIG.1F) Naive C57BL / 6 mice were vaccinated with Alum, AIsdB, Alum-ß-glucan (A-ß-glucan), A-ß-glucanIsdB, AlumTDB (ATDB) or ATDBIsdB and then SA challenge and tissue CFU counts as in FIG.1A (n=5-19). FIG.1G) SA-exposed C57BL / 6 mice were vaccinated with Alum, AIsdB, ATDB or ATDBIsdB and then SA challenge and tissue CFU counts as in FIG.1A (n=9). FIG.1H) SA-exposed C57BL / 6 mice were vaccinated with Alum, AIsdB, Alum-pertussis toxoid-IsdB (A-PtxIsdB) or Alum-Diphtheria toxoid-IsdB (A-DpthIsdB) and then SA challenge and tissue CFU counts as in FIG.1A. Data were from one to four independent experiments with each data point representing one mouse. Bars denote median. The data were analysed by Kruskal-Wallis non-parametric one-way ANOVA test. *<0.05, **<0.001, ***<0.0001, ns-non-significant.

[0012] FIG.s 2A-2H. Adjuvants mediate efficient protection in SA-exposed mice model. FIG. 2A) Naive C57BL / 6 mice or SA-exposed mice (3x at 7-D intervals) were vaccinated with Alum, AIsdB, CAF01 or CAF01IsdB (3x at 7-D intervals), then 14 days post-last vaccination, mice were challenged with SA (3.5x107CFU) followed by tissue CFU counts post 20 hr challenge (n=19-26). FIG.2B) Naive C57BL / 6 mice or SA-exposed mice were vaccinated with PBS, ß- glucan, or ß-glucanIsdB and then SA challenge and tissue CFU counts as in a. (n=3-10). FIG.s 2C, 2D) Naive C57BL / 6 mice or SA-exposed mice were vaccinated with TDB alone or TDBIsdB (FIG.2C) and TLR7 alone or TLR7IsdB (FIG.2D), then SA challenged and tissue CFU counts as in a (n=5-14). FIG.2E) Naive C57BL / 6 mice or SA-exposed mice were vaccinated with PBS, AS04 or AS04IsdB and then SA challenge and tissue CFU counts as in FIG.2A ((n=5-15). FIG.2F) Naive C57BL / 6 mice were vaccinated with Alum, AIsdB, Alum- ß-glucan (A-ß-glucan), A-ß-glucanIsdB, AlumTDB (ATDB) or ATDBIsdB and then SA challenge and tissue CFU counts as in FIG.2A (n=5-19). FIG.2G) SA-exposed C57BL / 6 mice were vaccinated with Alum, AIsdB, ATDB or ATDBIsdB and then SA challenge and tissue CFU counts as in FIG.2A (n=9). FIG.2H) SA-exposed C57BL / 6 mice were vaccinated with Alum, AIsdB, Alum-pertussis toxoid-IsdB (A-PtxIsdB) or Alum-Diphtheria toxoid-IsdB (A- DpthIsdB) and then SA challenge and tissue CFU counts as in FIG.2A. Data were from one to four independent experiments with each data point representing one mouse. Bars denote median. The data were analysed by Kruskal-Wallis non-parametric one-way ANOVA test. *<0.05, **<0.001, ***<0.0001, ns-non-significant.

[0013] FIG.s 3A-3B. Cytokine responses. FIG.3A) SA-exposed C57BL / 6 mice (3x at 7-D intervals) were vaccinated with IsdB plus adjuvant (3x at 7-D intervals), followed by isolation of splenocytes on D14 post-last immunization. Then splenocytes (pooled from 3 mice) were stimulated with IsdB antigen (10 µg / ml) for 2 days followed by cytokine ELISA on culture supernatant. FIG.3B) SA-exposed C57BL / 6 mice (3x at 7-D intervals) were vaccinated with Alum, AIsdB, AlumPtx or A-Ptx-IsdB (3x at 7-D intervals), followed by isolation of splenocytes on D14 post-last immunization. Then splenocytes were stimulated with IsdB antigen (10 µg / ml) for 2 days followed by cytokine ELISA on culture supernatant. Bars in FIG.3A denote mean±SD of three technical replicates of one independent experiment. Data in FIG.3B denote mean±SD of 10 technical replicates of one independent experiment. Data was analysed by one- way ANOVA with Tukey`s post-hoc test.

[0014] FIG.s 4A-4E. CAF01 mediated protection with other SA antigens and elicited long- lasting anti-SA immunity. FIG.s 4A-4B) Naïve (FIG.4A) or SA-exposed (FIG.4B) C57BL / 6 mice were vaccinated with Alum, AIsdB, AmntC or AIsdA, then 56 days post-last vaccination, mice were challenged with SA (3.5x107CFU) followed by tissue CFU counts in kidneys and spleen post 20 hr challenge. FIG.s 4C-4D) Naïve (FIG.4C) or SA-exposed (FIG.4D) C57BL / 6 mice were vaccinated with CAF01, CAF01IsdB, CAF01mntC or CAF01IsdA, then 56 days post-last vaccination, mice were challenged with SA (3.5x107CFU) followed by tissue CFU counts in kidneys and spleen post 20 hr challenge. FIG.4E) SA-exposed C57BL / 6 mice were vaccinated with CAF01 or CAF01FhuD2, then 85 days post-last vaccination, mice were challenged with SA (3.5x107CFU) followed by tissue CFU counts in kidneys and spleen post 20 hr challenge. Data were from one to four independent experiments with each data point representing one mouse. Bars denote median. The data were analysed by Kruskal-Wallis non- parametric one-way ANOVA test. *<0.05, **<0.001, ***<0.0001, ns-non-significant.

[0015] FIG.s 5A-6H. SA T cell imprints abrogate T cell protection from IsdB vaccination. FIG.5A) Experimental setting. muMt- or C57BL / 6 wild-type (WT) mice were either rested or intraperitoneally (i.p.) infected with 3x107SA (LAC) three times at 7-day intervals. Then mice were vaccinated i.p. with either alum or AlumIsdB (AIsdB) and challenged i.p. with SA (3x107) 7 days post-last vaccination (dpv). Bacterial burden in tissues was measured 20 h post-SA challenge. FIG.5B) Naïve or SA-exposed muMt- mice (n=9-12 per group) were vaccinated with either Alum or AIsdB, then SA challenged as in FIG.5A. FIG.5C) Naïve or SA-exposed WT mice (n=10-15 per group) were vaccinated with either Alum or AIsdB as in FIG.5A. Splenic CD3+T cells isolated on 14 dpv were adoptively transferred into naïve recipient mice, followed by SA challenge. FIG.5D) Naïve or SA-exposed muMt- mice (n=7-10 per group) were vaccinated with either TLR7 (Gardiquimod) alone or TLR7IsdB, then SA challenged as in FIG. 5A. FIG.5E) Splenic CD4+T cells (1x107) isolated from SA-exposed WT mice were adoptively transferred into naïve recipient WT mice. One day later, the recipient mice were vaccinated with either Alum or AIsdB (n=5-20 per group), followed by SA challenge as in FIG.5A. FIG.5F) Burden in tissue was measured. FIG.5G) SA-exposed splenic CD45.1 CD4+T cells (1x107) were transferred into naïve CD45.2 mice followed by AIsdB vaccination. Splenic CD45.1 or CD45.2 CD4+T cells were isolated from the vaccinated mice and transferred into naive recipient mice, vaccinated with Alum or AIsdB (n=7-10 per group) and SA challenged as in FIG.5A. FIG.5H) Burden in tissue was measured. Data were from two to four independent experiments with each data point representing one mouse. Bars denote median. The data were analyzed byKruskal-Wallis non-parametric one-way ANOVA test. *<0.05, **<0.01, ***0.001, ****<0.0001. ns-non-significant.

[0016] FIG.s 6A-6L. CD4+CD25+IL-10+T cells mediate IL10-dependent suppression of IsdB vaccine. FIG.6A) Splenocytes from naïve- or SA-exposed vaccinated mice were isolated on 14dpv and stimulated with IsdB (10 µg / ml) for 60 h, followed by IL-10 measurement in the supernatants (n=5 per group). FIG.6B) Mice were i.p. infected with SA (3x107CFU), then treated intravenously one day before and on the day of vaccination with either isotype IgG1 Ab or anti-IL-10 MAb.7 dpv, mice were challenged with SA. FIG.6C) Bacterial burden was measured 20 h post-challenge (n=9-10). FIG.6D) Experimental setting. Vert-X mice were untreated (NT) or exposed to SA, then SA challenged. Splenocytes were analyzed for eGFP (IL- 10) expressions by flow cytometry 20 h later. FIG.6E) Analysis of eGFP (IL-10) expression by adaptive immune cells from naïve and SA-exposed Vert-X mice post-SA challenge (n=5-7 per group). FIG.6F) Purified B or CD4+T cells from PBS or SA-exposed WT mice were stimulated with naïve splenocytes plus HKB (1:10) for 40 h. IL-10 ELISPOT assay (n=5 per group). FIG. 6G) Pooled purified B (n=5) or CD4+T cells (n=5) from SA-exposed vaccinated mice were stimulated with HKB (1:10) for 60 h. Culture supernatants were analyzed for IL-10. FIG.s 6H, 6I) Untreated or SA-exposed Vert-X mice were challenged with SA as shown in FIG.6D. Analysis of splenic eGFP+(IL-10) CD3+CD4+CD69+T cells (FIG.6H, n=5-7 per group) and CD3+CD4+CD25+T cells (FIG.6I, n=5-7 per group) 20 h after SA infection. FIG.6J) SA- exposed WT mice were depleted of either CD25+or CD69+T cells one day before vaccination, then challenged with SA (n=8-9 per group). FIG.6K) CD4+T cells isolated from WT mice, previously exposed to either Baker WT or IsdB / HarA double mutant, were adoptively transferred into naïve WT mice. The recipient mice were vaccinated, challenged with SA Baker (l, n=7-8 per group) as in FIG.1A). FIG.6L) Burden in tissue was measured. Data were from one to two independent experiments with each data point representing one mouse, except in FIG.6G. Bars denote median and the data in FIG.6G is represented as mean±SD of three technical replicates. Data in FIG.6A, 6B, 6D-6G were analyzed by one-way ANOVA with Tukey`s posthoc test, data in FIG.6H, 6I by non-parametric Mann-Whitney T test, while the data in FIG.6C, 6J-6L were analyzed by Kruskal-Wallis non-parametric one-way ANOVA test. *<0.05, **<0.01, ***<0.001, ****<0.0001. ns-non-significant.

[0017] FIG.s 7A-7E. IsdB vaccine suppression is dependent on STAT3 signaling, IL-10 and 10-R ^ expression on CD4+T cells. FIG.7A) Naïve or SA-exposed MIL-10- / -(IL10flox / floxxLysMcre) were vaccinated i.p. with either Alum or AIsdB, then challenged with SA on 7 dpv (n=5-6 per group). FIG.7B) SA-exposed CD4IL-10+ / +or CD4IL-10- / -were vaccinated i.p. with either Alum or AIsdB, then challenged with SA on 7 dpv (n=7-10 per group). FIG.7C) SA- exposed CD4IL10Rα+ / +or CD4IL10Rα- / -were vaccinated i.p. with either Alum or AIsdB, then challenged with SA on 7 dpv (n=3-5 per group). FIG.7D) SA-exposed WT mice were treated 1 day before, on the day of vaccination and 1 day after with either vehicle or an anti-STAT3 inhibitor, then challenged with SA on 7 dpv (n=5-9 per group). FIG.7E) SA-exposed WT mice were treated one day before and on the day of vaccination with either isotype IgG1 control or anti-IL-6 MAb, then challenged with SA on 7 dpv (n=13-15 per group). Data were from one to three independent experiments with each data point representing one mouse. Bars denote median. The data in FIG.s 7A, 7C-7D was analyzed by analyzed by one-way ANOVA with Tukey`s posthoc test, while the data in FIG.7B, 7E by Kruskal-Wallis non-parametric one-way ANOVA test. *<0.05, ***<0.001, ns-non-significant.

[0018] FIG.s 8A-8F. High potency IL-17A promoting adjuvants restore vaccine protection in SA-exposed mice. FIG.8A) SA-exposed WT mice were treated with either isotype IgG1 control or anti-IL-10 MAb before and on the day of AIsdB vaccination as in FIG.6B. Then, splenic CD4+T cells were purified 14 dpv and incubated with naïve splenocytes plus IsdB (10 µg / ml). IL-17A and IFN-γ from culture supernatant were measured at 60h (n=5 per group). FIG.8B, 8C) Naïve (FIG.8B, n=22-32 per group) or SA-exposed WT mice (FIG.8C, n=19-26 per group) were vaccinated i.p. with Alum, AIsdB, CAF01 or CAF01IsdB, then challenged with SA14 dpv. FIG.8D, 8E) Naïve (FIG.8D, n=9-14 per group) or SA-exposed WT mice (FIG.8E, n=9-14 per group) were vaccinated i.p. (3x, weekly apart) with Alum, AIsdB, AlumTDB (ATDB) or ATDBIsdB, then challenged with SA 14 dpv. FIG.8F) SA-exposed WT mice were vaccinated with either PBS or IsdB plus adjuvant. Splenocytes (pooled from three mouse) were purified 14 dpv and stimulated with IsdB (10 µg / ml) for 60 h, followed by analysis of supernatants for IL- 17A. Data were from one to 4 independent experiments with each data point representing one mouse, except in FIG.8F. Bars denote median in FIG.8A-8E and in FIG.8F data is represented as mean ± SD of three technical replicates of one independent experiment and repeated twice with similar results. The data in FIG.8A, 8F is analyzed by one-way ANOVA with Tukey`s post-hoc test while the data in FIG.s 8B-8E were analyzed by Kruskal-Wallis non- parametric one-way ANOVA test. *<0.05, **<0.01, ***<0.001, ****<0.0001 ns-non- significant.

[0019] FIG.s 9A-9G. IFN- ^ and IL-17A, independent of IL-10, confer IsdBCAF01 vaccine protection against SA in SA-exposed mice. FIG.9A) Serum (150 µl) collected 14dpv of SA- exposed vaccinated WT mice was transferred i.v. into naive mice. The recipient mice were challenged 20h after with SA (n=5 per group). FIG.9B) SA-exposed muMT- mice were vaccinated i.p. with Alum, AIsdB, CAF01 or CAF01IsdB, then challenged with SA 14 dpv (n=4- 7 per group per group). FIG.s 9C, 9D) SA-exposed WT mice were vaccinated i.p. with PBS, Alum, AIsdB, CAF01 or CAF01IsdB.14 dpv, splenic CD3+T cells (FIG.9C, n=8-11 per group) or CD4+T cells (FIG.9D, n=7-13 per group) were transferred i.v. into naïve WT mice. After 20h, the recipient mice were challenged with SA challenged. FIG.9E) SA-exposed WT mice were vaccinated i.p. with Alum, AIsdB, CAF01 or CAF01IsdB.14 dpv, splenocytes (1.5x106, n=5) were isolated and restimulated with IsdB antigen (10 µg / ml) for 48 h, followed by intracellular cytokine analysis by flow cytometry. FIG.9F) SA-exposed WT mice were vaccinated i.p. with PBS, CAF01 or CAF01IsdB. After 14d, the mice were treated with an isotype IgG1 control or anti-IFN-γ Mab, one day before and on the day of SA challenge (n=8-10 per group). FIG.9G) SA-exposed WT or IL-17- / -mice were vaccinated i.p. with Alum, AIsdB, CAF01 or CAF01IsdB, then SA challenged 14 dpv (n=3-9 per group). Data were from one to two independent experiments with each data point representing one mouse. Bars denote median. The data in FIG.9A, 9B, 9E, 9G were analyzed by one-way ANOVA with Tukey`s post-hoc test, while the data in FIG.9C, 9D, 9F by Kruskal-Wallis non-parametric one-way ANOVA test *<0.05, **<0.01, ****<0.001, ****<0.0001, ns-non-significant.

[0020] FIG.s 10A-10H. IL-10 mediates suppression and cross-suppression of SA vaccines in SA-exposed mice, but interference can be overcome by CAF01 FIG.10A) SA-exposed WT mice were treated with either isotype IgG1 Ab or anti-IL-10 MAb one day before and on the day of AFhuD2 vaccination (3x, weekly apart). The mice were SA challenged on 7dpv (n=10 per group). FIG.10B) SA-exposed WT mice were treated with either isotype IgG1 Ab or anti-IL-10 MAb one day before and on the day of AIsdBsdrE combination vaccine (3x, weekly apart). The mice were SA challenged on 7dpv (n=7-9 per group). FIG.10C) SA-exposed WT mice were vaccinated i.p. with CAF01 or CAF01IsdBsdrE, then challenged with SA 21 dpv (n=5 per group). FIG.s 10D-10E) Naïve (FIG.10D, n=10-23 per group) or SA-exposed WT mice (FIG. 10E, n=8-29 per group per group) were vaccinated i.p. with CAF01, CAF01IsdB, CAF01mntC or CAF01IsdA, then SA challenged on 56 dpv. FIG.10F) SA-exposed WT mice were vaccinated with CAF01 or CAF01FhuD2, then SA challenged 85 dpv (n=5-7 group). FIG.s 10G) WT mice were exposed to SA i.p., then subcutaneously vaccinated with Alum, AIsdB,CAF01 or CAF01IsdB (3x, weekly apart), then challenged with SA intradermal 7dpv. FIG. 10H) Skin lesions (n=10 per group) and CFU measured on 4 days after (n=5 per group). Data were from one to four independent experiments with each data point representing one mouse. Bars denote median. The data in FIG.s 10A, 10B, 10D-10E, 10G was analyzed by Kruskal- Wallis non-parametric one-way ANOVA test, data in c by one-way ANOVA test, while the data in FIG.s 10F, 10H by non-parametric unpaired Mann-Whitney T test. *<0.05, **<0.01, ***<0.001, ****<0.0001. ns-non-significant.

[0021] FIG.s 11A-11J. Prior SA exposure abrogates vaccine-induced protective T cell responses. FIG.11A) Serum from SA-exposed WT or muMt- AIsdB vaccinated mice was isolated on 7 dpv and analyzed for IsdB titers by an indirect ELISA (n=8 per group). FIG.11B) Naïve or SA-exposed muMt- mice (n=9-13 per group) were vaccinated with either Alum or AIsdB, then SA challenged as in FIG.5A. FIG.11C) Naïve or SA-exposed WT mice (n=10-15 per group) were vaccinated with either Alum or AIsdB as in FIG.5A. Splenic CD3+T cells isolated 14 dpv were adoptively transferred into naïve recipient mice, followed by SA challenge. FIG.11D) Naïve WT mice (n=8-9 per group) were vaccinated with either Alum or AIsdB, then SA challenged as in FIG.5A) (harvest of bacteria 20 h later). FIG.11E) Naïve mice (n=4-5 per group) were vaccinated with either Alum or AIsdB as in FIG.5A, then SA challenged. Bacterial burden in spleen, kidneys, and FIG.11F) peritoneum at 48 h post SA challenge. FIG.11G) Naive mice (n=8-10 per group) were vaccinated with either Alum or AIsdB as in FIG.5A, then one day before and on the day of SA challenge, were treated with isotype IgG, anti-CD4, anti- CD8 or anti-TCR. ð antibodies, then challenged with SA. FIG.11H) Naïve or SA-exposed muMt- mice (n=7-10 per group) were vaccinated with either TLR7 alone or TLR7IsdB, then SA challenged as in FIG.11A. FIG.11I) SA-exposed splenic CD4+T cells (1x107) were adoptively transferred into naïve recipient WT mice. One day later, the recipient mice were vaccinated with either Alum or AIsdB, and challenged with SA as in FIG.11A (n=5-20 per group). FIG.11J) SA-exposed splenic CD45.1 CD4+T cells (1x107) were transferred into naïve CD45.2 mice followed by AIsdB vaccination. Then, splenic CD45.1 or CD45.2 CD4+T cells were isolated 7 dpv and transferred into naive recipients, followed by vaccination and SA challenge of the recipients as in FIG.5E (n=7-10 per group). Data were from one to four independent experiments with each data point representing one mouse. Bars denote median. The data in FIG. 11A, 11E-11G were analyzed by non-parametric Mann-Whitney T test, while the data in FIG. 11B,-11D, 11H-11J were analyzed by Kruskal-Wallis non-parametric one-way ANOVA test*<0.05, **<0.01, ***<0.001, ****<0.0001. ns-non-significant.

[0022] FIG.s 12A-12C. IL-10 plays a critical role in vaccine suppression. FIG.12A) WT mice were either treated with PBS or SA (3x, 3x107CFU) and splenocytes (pooled, n=5, 1x106) were isolated on D7 post-SA exposure and were stimulated with either IsdB (10 µg / ml) or HKB (1:10). After 60 h of stimulation, culture supernatants were analyzed for IL-10. FIG.12B) Naïve or SA-exposed mice were vaccinated with AIsdB with or without anti-IL-10 MAb before and after vaccination, then challenged with SA (n=9-10 per group). FIG.12C) Experimental setting, and gating strategy for the measurement of IL-10 expression by adaptive immune cells. Vert-X mice were left untreated (NT) or exposed to SA (3x107CFU), then challenged with SA. eGFP (IL-10) expression in splenocytes was analyzed by flow cytometry after 20 h. Data were from one to two independent experiments with each data point representing one mouse in FIG.12A. Bars denote median, except in FIG.12A (represented as mean±SD of five technical replicates). The data in FIG.12A was analyzed by non-parametric Mann-Whitney T test, and the data in FIG.12B by Kruskal-Wallis non-parametric one-way ANOVA test. *<0.05, **<0.001, ns-non- significant.

[0023] FIG.s 13A-13E. CD4+CD25+IL-10+T cells, induced by SA exposure, mediate blunting of IsdB vaccine efficacy. FIG.13A) Percentage of splenic CD4+T, CD8+T and B220+B cells in naive or SA-exposed Vert-X mice assessed as in FIG.13B) (n=5-7 per group). FIG.13B) Purified B or CD4+T cells (1x105) from PBS or SA-exposed (3x, 3x107CFU) WT mice were stimulated with naïve splenocytes plus IsdB antigen (10µg / ml) for 40 h, followed by detection of IL-10 by an ELISPOT assay (n=5 per group). FIG.13C) Pooled purified B (n=5) or CD4+T cells (n=5) from Alum or AIsdB SA-exposed vaccinated mice were stimulated with IsdB (10 µg / ml) for 60 h, followed by IL-10 measurement from supernatants. FIG.13D) CD4+T cells were isolated from SA-exposed mice and transferred into naïve mice. The recipient mice were vaccinated in the presence of anti-IL10 Mab or isotype control (on day before and day of vaccination), then challenged with SA as in FIG.5A n=5-17 per group),FIG.13E) SA-exposed WT mice were depleted of either CD25+or CD69+T cells, vaccinated one day after, then SA challenged (n=8-9 per group). Data were from one to three independent experiments with each data point representing one mouse, except in FIG.13C). Bars denote median and the data in FIG.13C is pooled from five mouse represented as mean±SD of three technical replicates. Data in FIG.13A-13C were analyzed by one-way ANOVA with Tukey`s posthoc test, while the data in FIG.13D-13E were analyzed by Kruskal-Wallis non-parametric one-way ANOVA test. *<0.05, **<0.01, ***<0.001, ****<0.0001.

[0024] FIG.s 14A-14D. IL-10 released by CD4+T cells contribute directly to vaccine failure via IL-10Rα expressed on CD4+T cells. FIG.14A) Naïve or SA-exposed MIL-10- / -(IL10flox / floxx LysMcre) were vaccinated i.p. with either Alum or AIsdB, then challenged with SA 7 dpv (n=5-6 per group). FIG.14B) SA-exposed CD4IL-10+ / +or CD4IL-10- / -were vaccinated i.p. with either Alum or AIsdB, then challenged with SA 7 dpv (n=7-10 per group). FIG.14C) SA-exposed CD4IL10Rα+ / +and CD4IL10Rα- / -were vaccinated i.p. with either Alum or AIsdB, then challenged with SA 7 dpv (n=3-5 per group). FIG.14D) Splenocytes (pooled, n=5) from PBS- or SA-exposed (3 x 107CFU) WT mice were stimulated with either IsdB antigen (10 µg / ml) or HKB (1:10) in vitro. Cytokine IL-6 from supernatant was evaluated after 60h. FIG.14D) SA- exposed WT mice were treated with either isotype IgG1 control or anti-IL-6 MAb one day before and on the day of vaccination, then challenged with SA (n=13-15 per group).Data were from one to three independent experiments with each data point representing one mouse. Bars denote median, except in FIG.14D) (represented as mean±SD of five technical replicates). The data in FIG.14A-14C, 14E were analyzed by Kruskal-Wallis non-parametric one-way ANOVA test, while the data in FIG.14D was analyzed by non-parametric Mann-Whitney T test. *<0.05, **<0.01, ***<0.001, ns-non-significant.

[0025] FIG.s 15A-15B. Effect of IL-10 expressing CD4+T cell imprints on IL-17A, and the impact of adjuvants. FIG.15A) SA-exposed WT mice were treated with either isotype IgG1 control or anti-IL-10 MAb one day before and on the day of AIsdB vaccination as in Fig.2b. Splenic CD4+T cells were purified 14 dpv and incubated with naïve splenocytes plus HKB (1:10). After 60h, supernatants were assayed for IL-17A and IFN-γ (n=5 per group). FIG.15B) Splenocytes were isolated from WT mice exposed to SA 7 days after the last SA exposure. The cells were stimulated with various adjuvants (10 µg / well) in vitro and IL-17A analysis was performed from supernatants after 60h (pooled, n=5 per group). Data were from one experiment with each data point representing one mouse in FIG.15A and each dot in FIG.15B is a technical replicate. Bars denote median in FIG.15A while in FIG.15B data is represented as mean ± SD of three technical replicates of one independent experiment. The data were analyzed by one-way ANOVA with Tukey`s post-hoc test. *<0.05, **<0.01, ****<0.0001, ns-non- significant.

[0026] FIG.s 16A-16H. High potency IL-17A adjuvants restore vaccine protection in SA- exposed mice. FIG.16A, 16B) Naïve (FIG.16A, n=22-32 per group) or SA-exposed WT mice (FIG.16B, n=19-26 per group) were vaccinated i.p. with Alum, AIsdB, CAF01 or CAF01IsdB,followed by SA challenge 14 dpv. FIG.16C) Naïve and SA-exposed WT mice were vaccinated i.p. with TDB alone or TDBIsdB, then challenged with SA 14 dpv (n=5-10 per group). FIG. 16D, 16E) Naïve (FIG.16D, n=9-14) or SA-exposed WT mice (FIG.16E, n=9-14) were vaccinated i.p. with Alum, AIsdB, AlumTDB (ATDB) or ATDBIsdB, followed by SA challenge 14 dpv. FIG.16F, 16G) Naïve (FIG.16F, n=10) or SA-exposed WT mice (FIG.16G, n=3-10) were vaccinated i.p. with beta-glucan or beta-glucanIsdB, then SA challenged on 14 dpv. FIG. 16H) Naïve (n=10) or SA-exposed WT mice (n=14-15) were vaccinated i.p. with TLR7 agonist or TLR7 agonist plus IsdB, followed by SA challenge on 14 dpv. Data were from one to 4 independent experiments with each data point representing one mouse. Bars denote median. The data were analyzed by Kruskal-Wallis non-parametric one-way ANOVA test. *<0.05, **<0.01, ***<0.001, ****<0.0001. ns-non-significant.

[0027] FIG.s 17A-17D. IL-17A responses correlate with vaccine protection in SA-exposed mice. FIG.17A) SA-exposed WT mice were vaccinated i.p. with Alum, AIsdB, Alum- diphtheria toxoid-IsdB (A-DpthIsdB) or A-PtxIsdB, then challenged with SA 14 dpv (n=10-20 per group). FIG.17B) Naïve WT mice were vaccinated i.p. with A-Ptx or A-PtxIsdB, then SA challenged 14 dpv (n=10-20 per group). FIG.17C) SA-exposed (3x, 3x107CFU) WT mice were vaccinated i.p. with either PBS or IsdB plus adjuvant. Splenocytes (pooled from three mouse) purified on 14 dpv were stimulated with IsdB (10 µg / ml), and culture supernatants were analyzed for IL-17A after 60h. FIG.17D) SA-exposed WT mice were vaccinated i.p. with Alum, AIsdB, Alum-pertussis toxoid (A-Ptx) or A-PtxIsdB. Splenocytes purified on 14 dpv were stimulated with IsdB (10 µg / ml), and culture supernatants were analyzed for IL-17A after 60h (n=10 per group). Data were from one to 3 independent experiments with each data point representing one mouse, except in FIG.17B. Bars denote median in FIG.17A, 17B, 17D, and in FIG.17C data is represented as mean ± SD of three technical replicates of one independent experiment and repeated twice with similar results. The data in FIG.17A, 17D by analyzed by Kruskal-Wallis non-parametric one-way ANOVA test, data in FIG.17B by non-paired Mann-Whitney T test, while the data in c by one-way ANOVA with Tukey`s post-hoc test, *<0.05, **<0.01, ***<0.001, ****<0.0001 ns-non-significant

[0028] FIG.s 18A-18H. S8 Th17 adjuvants induce vaccine protection in SA-exposed mice that is CD4+T cell dependent. FIG.s 18A, 18B) Serum (150 µl) collected 14dpv of naïve (FIG.18A, n=10 per group) or SA-exposed (FIG.18B, n=5 per group) WT mice was transferred i.v. into naive recipient mice. After 20h, the mice were challenged with SA (n=5 per group). FIG.18C)IgG titers (diluted 1:100000) of serum collected 14 dpv from SA-exposed vaccinated mice (n=5 per group). FIG.18D) SA-exposed muMT- mice were vaccinated i.p. with Alum, AIsdB, CAF01 or CAF01IsdB, then SA challenged 14 dpv (n=4-7 per group per group). FIG.18E, 18F) SA-exposed WT mice were vaccinated i.p. with Alum, AIsdB, CAF01 or CAF01IsdB.14 dpv, splenic CD3+T cells (FIG.18E, n=8-11 per group) or CD4+T cells (FIG.18F, n=7-13 per group) were isolated and i.v. transferred into naïve WT mice, followed by SA challenge of the recipient mice after 20 h. FIG.18G) SA-exposed WT mice were vaccinated i.p. with Alum, AIsdB, ATDB or ATDBIsdB.14 dpv, splenic CD4+T cells were isolated and transferred i.v. into naïve WT mice, followed by SA challenge of the mice after 20 h (n=3-4 per group). FIG.18H) Gating strategy for the detection of intracellular cytokines. Data were from one to two independent experiments with each data point representing one mouse. Bars denote median. The data were analyzed by one-way ANOVA with Tukey`s post-hoc test. *<0.05, **<0.01, ****<0.001, ****<0.0001, ns-non-significant.

[0029] FIG.s 19A-19D. CAF01 adjuvant induces IL-17A and IFN- ^ dependent protection in SA-exposed mice. FIG.19A) SA-exposed WT mice were vaccinated i.p. with Alum, AIsdB, CAF01 or CAF01IsdB.14 dpv, splenocytes (1x106, n=5, pooled) were isolated and stimulated with IsdB antigen (10 µg / ml) for 60 h, and cytokines from culture supernatants were analyzed. Bars denote mean ± SD of three technical replicates of one experiment and the experiment was repeated twice. FIG.19B) SA-exposed WT mice were vaccinated i.p. with CAF01 or CAF01IsdB.14 dpv, the mice were treated with an isotype IgG1 control or anti-IFN-γ MAb one day before and on the day of SA challenge (n=8-10 per group). FIG.19C) SA-exposed WT or IL-17- / -mice were vaccinated i.p. with Alum, AIsdB, CAF01 or CAF01IsdB, then challenged with SA 14 dpv (n=3-9 per group). FIG.19D) SA-exposed WT mice were vaccinated i.p. withCAF01 or CAF01IsdB.14 dpv, the mice were treated with an isotype IgG1 control or anti- IL-17A MAb one day before and on the day of SA challenge (n=p-10 per group). Data were from one to two independent experiments with each data point representing one mouse in FIG. 19B-19D and bars denote median. The data in FIG.19A, 19C was analyzed by one-way ANOVA test with Tukey`s post-hoc test, while the data in FIG.19B, 19D by Kruskal-Wallis non-parametric one-way ANOVA test. *<0.05, **<0.01, ***<0.001, ****<0.0001. ns-non- significant.

[0030] FIG.s 20A-20H. CAF01 adjuvant induces long lasting protection against multiple strains of SA. FIG.20A) SA-exposed WT mice were vaccinated i.p. with Alum or combinationAIsdBsdrE vaccine, then SA challenged (n=10 per group). FIG.20B) SA-exposed WT mice were vaccinated i.p. with PBS, CAF01 or CAF01IsdBsdrE, then challenged with SA 21 dpv (n=5 per group). FIG.20C, 20D) Naïve (FIG.20C, n=10-23 per group) or SA-exposed WT mice (FIG.20D, n=8-29 per group per group) were vaccinated i.p. with PBS, CAF01, CAF01IsdB, CAF01mntC or CAF01IsdA, followed by SA challenge 56 dpv. FIG.20E) SA- exposed WT mice were vaccinated i.p. with CAF01 or CAF01FhuD2, followed by SA challenge 85 dpv (n=5-7 group). FIG.20F, 20G) SA (Newman FIG.20F or SA113 FIG.20G-exposed WT mice (3x, 3x107CFU) were vaccinated i.p. with CAF01 or CAF01IsdB, followed by challenge with the same SA strain on 85 dpv (n=5 per group). FIG.20H) SA-exposed WT male mice were vaccinated i.p. with CAF01 or CAF01IsdB, then SA challenge 14 dpv (n=5-7 group). Data were from one to four independent experiments with each data point representing one mouse. Bars denote median. The data in FIG.20A, 20E a,e was analyzed by non-parametric unpaired Mann-Whitney T test, data in FIG.20B, 20F-20H by one-way ANOVA test, while the data in FIG.20C-20D by Kruskal-Wallis non-parametric one-way ANOVA test. *<0.05, **<0.001, ***<0.0001, ns-non-significant.

[0031] FIG.s 21A-21B. Naïve or SA-exposed Mice were vaccinated with either PBS, curdlan or curdlan IsdB as previously described, then challenged with SA on day 14 post-last vaccination. Bacterial burden in FIG.21A) kidneys and FIG.21B) spleen were assessed post- challenge.

[0032] FIG.s 22A-22C. Select adjuvants induced potent IL-17 responses. FIG.22A) Mice were exposed to SA at days 1, 8 and 14. Splenocytes from the SA-exposed mice were purified on day 21 following exposure. The mice were then stimulated in vitro with an adjuvant. IL-17 detection was then completed by ELISA. FIG.22B) Mice were exposed to SA. SA-exposed mice were vaccinated with an adjuvant + IsdB at days 1, 8 and 14. Splenocytes were purified on day 14 post-last vaccination and stimulated with IsdB antigen. FIG.22C) IL-17 detection was then completed by ELISA.

[0033] FIG.s 23A-23B). Mice were vaccinated with compositions including Alum+MPLA (AS04). Naïve or SA-exposed Mice were vaccinated with either PBS, AS04 or AS04+IsdB as previously described, then challenged with SA on day 14 post-last vaccination. Bacterial burden in FIG.23A) kidneys and FIG.23B) spleen post-challenge. DETAILED DESCRIPTION

[0034] While various embodiments and aspects of the present invention are shown and described herein, it will be obvious to those skilled in the art that such embodiments and aspects are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention.

[0035] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in the application including, without limitation, patents, patent applications, articles, books, manuals, and treatises are hereby expressly incorporated by reference in their entirety for any purpose.

[0036] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art. See, e.g., Singleton et al., DICTIONARY OF MICROBIOLOGY AND MOLECULAR BIOLOGY 2nd ed., J. Wiley & Sons (New York, NY 1994); Sambrook et al., MOLECULAR CLONING, A LABORATORY MANUAL, Cold Springs Harbor Press (Cold Springs Harbor, NY 1989). Any methods, devices and materials similar or equivalent to those described herein can be used in the practice of this invention. The following definitions are provided to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.

[0037] The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an α carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid. The terms “non-naturallyoccurring amino acid” and “unnatural amino acid” refer to amino acid analogs, synthetic amino acids, and amino acid mimetics which are not found in nature.

[0038] The term “amino acid side chain” refers to the functional substituent contained on amino acids. For example, an amino acid side chain may be the side chain of a naturally occurring amino acid. Naturally occurring amino acids are those encoded by the genetic code (e.g., alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, or valine), as well as those amino acids that are later modified, e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. In embodiments, the amino acid side chain may be a non-natural amino acid side chain. In embodiments, the amino acid side .symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.

[0040] The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues, wherein the polymer may In embodiments be conjugated to a moiety that does not consist of amino acids. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers.

[0041] The term "recombinant" when used with reference, for example, to a cell, a nucleic acid, a protein, or a vector, indicates that the cell, nucleic acid, protein or vector has been modified by or is the result of laboratory methods. Thus, for example, recombinant proteins (e.g. a recombinant non-toxin SA antigen protein) include proteins produced by laboratory methods. Recombinant proteins can include amino acid residues not found within the native (non- recombinant) form of the protein or can be include amino acid residues that have been modified, e.g., labeled.

[0042] The term "heterologous" when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).

[0043] A "fusion protein" refers to a chimeric protein encoding two or more separate protein sequences that are recombinantly expressed as a single moiety. Because the different proteins in fusion proteins may affect the functionality of other proteins under certain circumstances, peptide linkers may be used between different proteins within the same fusion protein. These peptide linkers may have a flexible structure and separate the proteins within the fusion protein so that each protein in the fusion proteins substantially retains its function. Peptide linkers are known in the art and described, for example, in Chen et al, Adv Drug Deliv Rev, 65(10);1357- 1369 (2013).

[0044] An amino acid or nucleotide base "position" is denoted by a number that sequentially identifies each amino acid (or nucleotide base) in the reference sequence based on its position relative to the N-terminus (or 5'-end). Due to deletions, insertions, truncations, fusions, and the like that must be taken into account when determining an optimal alignment, in general the amino acid residue number in a test sequence determined by simply counting from the N- terminus will not necessarily be the same as the number of its corresponding position in the reference sequence. For example, in a case where a variant has a deletion relative to an aligned reference sequence, there will be no amino acid in the variant that corresponds to a position in the reference sequence at the site of deletion. Where there is an insertion in an aligned referencesequence, that insertion will not correspond to a numbered amino acid position in the reference sequence. In the case of truncations or fusions there can be stretches of amino acids in either the reference or aligned sequence that do not correspond to any amino acid in the corresponding sequence.

[0045] The terms "numbered with reference to" or "corresponding to," when used in the context of the numbering of a given amino acid or polynucleotide sequence, refers to the numbering of the residues of a specified reference sequence when the given amino acid or polynucleotide sequence is compared to the reference sequence. An amino acid residue in a protein "corresponds" to a given residue when it occupies the same essential structural position within the protein as the given residue. One skilled in the art will immediately recognize the identity and location of residues corresponding to a specific position in a protein in other proteins with different numbering systems. For example, by performing a simple sequence alignment with a protein the identity and location of residues corresponding to specific positions of the protein are identified in other protein sequences aligning to the protein. For example, a selected residue in a selected protein corresponds to glutamic acid at position 138 when the selected residue occupies the same essential spatial or other structural relationship as a glutamic acid at position 138. In some embodiments, where a selected protein is aligned for maximum homology with a protein, the position in the aligned selected protein aligning with glutamic acid 138 is the to correspond to glutamic acid 138. Instead of a primary sequence alignment, a three dimensional structural alignment can also be used, e.g., where the structure of the selected protein is aligned for maximum correspondence with the glutamic acid at position 138, and the overall structures compared. In this case, an amino acid that occupies the same essential position as glutamic acid 138 in the structural model is the to correspond to the glutamic acid 138 residue.

[0046] "Conservatively modified variants" applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, "conservatively modified variants" refers to those nucleic acids that encode identical or essentially identical amino acid sequences. Because of the degeneracy of the genetic code, a number of nucleic acid sequences will encode any given protein. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are "silent variations," which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide alsodescribes every possible silent variation of the nucleic acid. One of skill will recognize that each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, each silent variation of a nucleic acid which encodes a polypeptide is implicit in each described sequence.

[0047] As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the disclosure.

[0048] The following eight groups each contain amino acids that are conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton, Proteins (1984)).

[0049] The terms "identical" or percent "identity," in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 60% identity, preferably 65%, 70%, 75%, 75%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,97%, 98%, 99%, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection (see, e.g., NCBI web site http: / / www.ncbi.nlm.nih.gov / BLAST / or the like). Such sequences are then said to be "substantially identical." This definition also refers to, or may be applied to, the compliment of a test sequence. The definition also includes sequences that have deletions and / or additions, as well as those that have substitutions. The preferred algorithms can account for gaps and the like. Preferably, identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.

[0050] "Percentage of sequence identity" is determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity.

[0051] An amino acid or nucleotide base "position" is denoted by a number that sequentially identifies each amino acid (or nucleotide base) in the reference sequence based on its position relative to the N-terminus (or 5'-end). Due to deletions, insertions, truncations, fusions, and the like that must be taken into account when determining an optimal alignment, in general the amino acid residue number in a test sequence determined by simply counting from the N- terminus will not necessarily be the same as the number of its corresponding position in the reference sequence. For example, in a case where a variant has a deletion relative to an aligned reference sequence, there will be no amino acid in the variant that corresponds to a position in the reference sequence at the site of deletion. Where there is an insertion in an aligned reference sequence, that insertion will not correspond to a numbered amino acid position in the reference sequence. In the case of truncations or fusions there can be stretches of amino acids in either the reference or aligned sequence that do not correspond to any amino acid in the corresponding sequence.

[0052] A "comparison window", as used herein, includes reference to a segment of any one of the number of contiguous positions selected from the group consisting of, e.g., a full length sequence or from 20 to 600, about 50 to about 200, or about 100 to about 150 amino acids or nucleotides in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman (1970) Adv. Appl. Math.2:482c, by the homology alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol.48:443, by the search for similarity method of Pearson and Lipman (1988) Proc. Nat’l. Acad. Sci. USA 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by manual alignment and visual inspection (see, e.g., Ausubel et al., Current Protocols in Molecular Biology (1995 supplement)).

[0053] An example of an algorithm that is suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1977) Nuc. Acids Res.25:3389-3402, and Altschul et al. (1990) J. Mol. Biol. 215:403-410, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (http: / / www.ncbi.nlm.nih.gov / ). This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always > 0) and N (penalty score for mismatching residues; always < 0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. TheBLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, an expectation (E) or 10, M=5, N=-4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a word length of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff and Henikoff (1989) Proc. Natl. Acad. Sci. USA 89:10915) alignments (B) of 50, expectation (E) of 10, M=5, N=-4, and a comparison of both strands.

[0054] The BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin and Altschul (1993) Proc. Natl. Acad. Sci. USA 90:5873-5787). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, more preferably less than about 0.01, and most preferably less than about 0.001.

[0055] For specific proteins described herein, the named protein includes any of the protein’s naturally occurring forms, variants or homologs that maintain activity of the protein (e.g., within at least 50%, 75%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to the native protein). In some embodiments, variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring form. In other embodiments, the protein is the protein as identified by its NCBI sequence reference. In other embodiments, the protein is the protein as identified by its NCBI sequence reference, homolog or functional fragment thereof.

[0056] The terms “linker” or “peptide linker” as used herein refer to short amino acid or peptide sequences that occur between protein domains. Linkers are often composed of flexible amino acids such as glycine (G) and / or serine (S), and allow a relative freedom of movement to adjacent protein domains. Linkers can be used when it is necessary to ensure that two adjacent domains do not sterically interfere with one another.

[0057] The term "antibody" refers to a polypeptide encoded by an immunoglobulin gene or functional fragments thereof that specifically binds and recognizes an antigen. The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Light chains areclassified as either kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively.

[0058] The terms “antigen” and “epitope” interchangeably refer to the portion of a molecule (e.g., a polypeptide) which is specifically recognized by a component of the immune system, e.g., an antibody, a T cell receptor, or other immune receptor such as a receptor on natural killer (NK) cells. As used herein, the term “antigen” encompasses antigenic epitopes and antigenic fragments thereof.

[0059] An exemplary immunoglobulin (antibody) structural unit can have a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one “light” (about 25 kDa) and one “heavy” chain (about 50-70 kDa). The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms “variable heavy chain,” “VH,” or “VH” refer to the variable region of an immunoglobulin heavy chain, including an Fv, scFv , dsFv or Fab; while the terms “variable light chain,” “VL” or “VL” refer to the variable region of an immunoglobulin light chain, including an Fv, scFv , dsFv or Fab.

[0060] Examples of antibody functional fragments include, but are not limited to, complete antibody molecules, antibody fragments, such as Fv, single chain Fv (scFv), complementarity determining regions (CDRs), VL (light chain variable region), VH (heavy chain variable region), Fab, F(ab)2' and any combination of those or any other functional portion of an immunoglobulin peptide capable of binding to target antigen (see, e.g., FUNDAMENTAL IMMUNOLOGY (Paul ed., 4th ed.2001). As appreciated by one of skill in the art, various antibody fragments can be obtained by a variety of methods, for example, digestion of an intact antibody with an enzyme, such as pepsin; or de novo synthesis. Antibody fragments are often synthesized de novo either chemically or by using recombinant DNA methodology. Thus, the term antibody, as used herein, includes antibody fragments either produced by the modification of whole antibodies, or those synthesized de novo using recombinant DNA methodologies (e.g., single chain Fv) or those identified using phage display libraries (see, e.g., McCafferty et al., (1990) Nature 348:552). The term "antibody" also includes bivalent or bispecific molecules, diabodies, triabodies, and tetrabodies. Bivalent and bispecific molecules are described in, e.g., Kostelny et al. (1992) J. Immunol.148:1547, Pack and Pluckthun (1992) Biochemistry 31:1579, Hollinger et al.( 1993), PNAS. USA 90:6444, Gruber et al. (1994) J Immunol.152:5368, Zhu et al. (1997)Protein Sci.6:781, Hu et al. (1996) Cancer Res.56:3055, Adams et al. (1993) Cancer Res. 53:4026, and McCartney, et al. (1995) Protein Eng.8:301.

[0061] The term "isolated", when applied to a nucleic acid or protein, denotes that the nucleic acid or protein is essentially free of other cellular components with which it is associated in the natural state. It can be, for example, in a homogeneous state and may be in either a dry or aqueous solution. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. A protein that is the predominant species present in a preparation is substantially purified.

[0062] A “cell” as used herein, refers to a cell carrying out metabolic or other function sufficient to preserve or replicate its genomic DNA. A cell can be identified by well-known methods in the art including, for example, presence of an intact membrane, staining by a particular dye, ability to produce progeny or, in the case of a gamete, ability to combine with a second gamete to produce a viable offspring. Cells may include prokaryotic and eukaroytic cells. Prokaryotic cells include but are not limited to bacteria. Eukaryotic cells include but are not limited to yeast cells and cells derived from plants and animals, for example mammalian, insect (e.g., spodoptera) and human cells. Cells may be useful when they are naturally nonadherent or have been treated not to adhere to surfaces, for example by trypsinization.

[0063] “B Cells” or “B lymphocytes” are used in accordance to their plain ordinary meaning in the art and are lymphocytes, a type of white blood cell (leukocyte), that develops into a plasma cell (a “mature B cell”), which produces antibodies. An “immature B cell” is a cell that can develop into a mature B cell. Generally, pro-B cells undergo immunoglobulin heavy chain rearrangement to become pro B pre B cells, and further undergo immunoglobulin light chain rearrangement to become an immature B cells. Immature B cells include T1 and T2 B cells.

[0064] “T cells” or “T lymphocytes” are used in accordance to their plain ordinary meaning in the art and are a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells, by the presence of a T-cell receptor on the cell surface. T cells include, for example, natural killer T (NKT) cells, cytotoxic T lymphocytes (CTLs), regulatory T (Treg) cells, and T helper cells. Different types of T cells can be distinguished by use of T cell detection agents.

[0065] A "memory T cell" is used in accordance to its plain ordinary meaning in the art and is a T cell that has previously encountered and responded to its cognate antigen during prior infection previous vaccination. At a second encounter with its cognate antigen memory T cells can reproduce (divide) to mount a faster and stronger immune response than the first time the immune system responded to the pathogen.

[0066] A "regulatory T cell" or "suppressor T cell" is a lymphocyte which modulates the immune system, maintains tolerance to self-antigens, and prevents autoimmune disease.

[0067] As used herein, the terms “natural killer cells” and “NK cells” are used in accordance with their plain ordinary meaning and refer to a type of cytotoxic lymphocyte involved in the innate immune system. The role NK cells play is typically analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells may provide rapid responses to infected cells, acting at around 3 days after infection. Typically, immune cells detect major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing lysis or apoptosis. NK cells typically have the ability to recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. In embodiments, NK cells are identified by the presence of CD56 and the absence of CD3. NK cells may be capable of recognizing and killing stressed cells in the absence of antibodies and MHC.

[0068] Staphylococcus aureus, also referred to as SA, S. aureus, Staph aureus, or Staph a, is a gram-positive bacterium and is a member of the family bacillota. SA is a coccal bacterium and can arrange in clusters. SA reproduces asexually by binary fission, can grow aerobically or anaerobically (facultative), and at temperatures between 18 C and 40 C. SA can be present in human hosts in the upper respiratory tract, gut mucosa and skin as part of the normal microbiota. However, SA, can cause disease in conditions common in community-acquired and hospital- acquired settings, and in susceptible subjects. SA is a cause of bacteremia and infective endocarditis, and various skin and soft-tissue infections. Drug resistance strains of SA have emerged, generating multi-drug resistant strains including MRSA (Methicillin-Resistant Staphylococcus aureus).

[0069] “Biological sample” or “sample” refer to materials obtained from or derived from a subject or patient. A biological sample includes sections of tissues such as biopsy and autopsy samples, and frozen sections taken for histological purposes. Such samples include bodily fluids such as blood and blood fractions or products (e.g., serum, plasma, platelets, red blood cells, andthe like), sputum, tissue, cultured cells (e.g., primary cultures, explants, and transformed cells) stool, urine, synovial fluid, immune cells, hematopoietic cells, fibroblasts, macrophages, T cells, etc. A biological sample is typically obtained from a eukaryotic organism, such as a mammal such as a primate e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat, mouse; rabbit; or a bird; reptile; or fish.

[0070] "Contacting" is used in accordance with its plain ordinary meaning and refers to the process of allowing at least two distinct species (e.g. chemical compounds including biomolecules or cells) to become sufficiently proximal to react, interact or physically touch. It should be appreciated; however, the resulting reaction product can be produced directly from a reaction between the added reagents or from an intermediate from one or more of the added reagents which can be produced in the reaction mixture.

[0071] The term "contacting" may include allowing two species to react, interact, or physically touch, wherein the two species may be, for example, a compound as described herein and a steric hindering chemical moiety. In embodiments contacting includes, allowing a vaccine composition described herein to interact with a cell. In embodiments contacting includes, allowing a vaccine composition described herein to interact with an SA bacterium.

[0072] “Control” or “control experiment” is used in accordance with its plain ordinary meaning and refers to an experiment in which the subjects or reagents of the experiment are treated as in a parallel experiment except for omission of a procedure (e.g. administering the vaccine provided herein), reagent (e.g. vaccine composition provided herein), or variable of the experiment. In some instances, the control is used as a standard of comparison in evaluating experimental effects. In some embodiments, a control is the measurement of the activity of a protein (e.g. IL-17, IFN-γ) or level of a protein (e.g. IL-17, IFN-γ, a neutralizing antibody) in the absence of a composition (e.g. vaccine composition) as described herein (including embodiments and examples). In embodiments, a control is the measurement of IL-17 expression, IL-17 activity, or IL-17 secretion from a cell in the absence of the vaccine provided herein, including embodiments thereof. In embodiments, a control is the measurement of IFN-γ expression, IFN-γ activity, or IFN-γ secretion from a cell in the absence of the vaccine provided herein, including embodiments thereof. In embodiments, a control is the measurement of production of a neutralizing antibody targeting a non-toxin SA antigen in the absence of the vaccine provided herein, including embodiments thereof. In embodiments, a control is the measurement ofproduction of a neutralizing antibody targeting a toxin SA antigen in the absence of the vaccine provided herein, including embodiments thereof.

[0073] A “control” or “standard control” refers to a sample, measurement, or value that serves as a reference, usually a known reference, for comparison to a test sample, measurement, or value. For example, a test sample can be taken from a patient suspected of having a given disease (e.g. SA-associated disease) or condition (e.g. SA infection) and compared to a known normal (non-diseased, non-infected) individual (e.g. a standard control subject). A standard control can also represent an average measurement or value gathered from a population of similar individuals (e.g. standard control subjects) that do not have a given disease (i.e. standard control population), e.g., healthy individuals with a similar medical background, same age, weight, etc. A standard control value can also be obtained from the same individual, e.g. from an earlier-obtained sample from the patient prior to disease onset. For example, a control can be devised to compare therapeutic benefit based on pharmacological data (e.g., half-life) or therapeutic measures (e.g., comparison of side effects). Controls are also valuable for determining the significance of data. For example, if values for a given parameter are widely variant in controls, variation in test samples will not be considered as significant. One of skill will recognize that standard controls can be designed for assessment of any number of parameters (e.g. RNA levels, protein levels, specific cell types, specific bodily fluids, specific tissues, etc). One of skill in the art will understand which standard controls are most appropriate in a given situation and be able to analyze data based on comparisons to standard control values. Standard controls are also valuable for determining the significance (e.g. statistical significance) of data. For example, if values for a given parameter are widely variant in standard controls, variation in test samples will not be considered as significant.

[0074] The terms “treating”, or “treatment” refers to any indicia of success in the therapy or amelioration of an injury, disease, pathology or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; improving a patient’s physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters; including the results of a physical examination, neuropsychiatric exams, and / or a psychiatric evaluation. The term "treating" and conjugations thereof may includeprevention of an injury, pathology, condition, or disease. In embodiments, treating is preventing. In embodiments, treating does not include preventing.

[0075] “Treating” or “treatment” as used herein (and as well-understood in the art) also broadly includes any approach for obtaining beneficial or desired results in a subject’s condition, including clinical results. Beneficial or desired clinical results can include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, diminishment of the extent of a disease, stabilizing (i.e., not worsening) the state of disease, prevention of a disease’s transmission or spread, delay or slowing of disease progression, amelioration or palliation of the disease state, diminishment of the reoccurrence of disease, and remission, whether partial or total and whether detectable or undetectable. In other words, "treatment" as used herein includes any cure, amelioration, or prevention of a disease. Treatment may prevent the disease from occurring; inhibit the disease’s spread; relieve the disease’s symptoms (e.g., ocular pain, seeing halos around lights, red eye, very high intraocular pressure), fully or partially remove the disease’s underlying cause, shorten a disease’s duration, or do a combination of these things.

[0076] "Treating" and "treatment" as used herein include prophylactic treatment. Treatment methods include administering to a subject a therapeutically effective amount of an active agent. The administering step may consist of a single administration or may include a series of administrations. The length of the treatment period depends on a variety of factors, such as the severity of the condition, the age of the patient, the concentration of active agent, the activity of the compositions used in the treatment, or a combination thereof. It will also be appreciated that the effective dosage of an agent used for the treatment or prophylaxis may increase or decrease over the course of a particular treatment or prophylaxis regime. Changes in dosage may result and become apparent by standard diagnostic assays known in the art. In some instances, chronic administration may be required. For example, the compositions are administered to the subject in an amount and for a duration sufficient to treat the patient. In embodiments, the treating or treatment is no prophylactic treatment.

[0077] The term “prevent” refers to a decrease in the occurrence of disease symptoms in a patient. As indicated above, the prevention may be complete (no detectable symptoms) or partial, such that fewer symptoms are observed than would likely occur absent treatment.

[0078] The term "associated" or "associated with" in the context of a substance or substance activity or function associated with a disease (e.g., an SA-associated disease) means that the disease (e.g. pneumonia, abscess, blood infection, food poisoning, etc.) is caused by (in whole orin part), or a symptom of the disease is caused by (in whole or in part) the substance or substance activity or function (e.g. infection and / or exposure to SA).

[0079] A “effective amount” is an amount sufficient for a compound to accomplish a stated purpose relative to the absence of the compound (e.g. achieve the effect for which it is administered, treat a disease associated with SA infection, or reduce one or more symptoms of a disease or condition associated with SA infection, treat SA infection, prevent SA infection). An example of an “effective amount” is an amount sufficient to contribute to the treatment, prevention, or reduction of a symptom or symptoms of a disease, which could also be referred to as a “therapeutically effective amount.” A “reduction” of a symptom or symptoms (and grammatical equivalents of this phrase) means decreasing of the severity or frequency of the symptom(s), or elimination of the symptom(s). A “prophylactically effective amount” of a drug is an amount of a drug that, when administered to a subject, will have the intended prophylactic effect, e.g., preventing or delaying the onset (or reoccurrence) of an injury, disease, pathology or condition, or reducing the likelihood of the onset (or reoccurrence) of an injury, disease, pathology, or condition, or their symptoms. The full prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a prophylactically effective amount may be administered in one or more administrations. The exact amounts will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols.1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins).

[0080] For any composition described herein, the therapeutically effective amount can be initially determined from cell culture assays. Target concentrations will be those concentrations of active compound(s) that are capable of achieving the methods described herein, as measured using the methods described herein or known in the art.

[0081] As is well known in the art, therapeutically effective amounts for use in humans can also be determined from animal models. For example, a dose for humans can be formulated to achieve a concentration that has been found to be effective in animals. The dosage in humans can be adjusted by monitoring compounds effectiveness and adjusting the dosage upwards or downwards, as described above. Adjusting the dose to achieve maximal efficacy in humansbased on the methods described above and other methods is well within the capabilities of the ordinarily skilled artisan.

[0082] The term “therapeutically effective amount,” as used herein, refers to that amount of the therapeutic agent sufficient to ameliorate the disorder, as described above. For example, for the given parameter, a therapeutically effective amount will show an increase or decrease of at least 5%, 10%, 15%, 20%, 25%, 40%, 50%, 60%, 75%, 80%, 90%, or at least 100%. Therapeutic efficacy can also be expressed as “-fold” increase or decrease. For example, a therapeutically effective amount can have at least a 1.2-fold, 1.5-fold, 2-fold, 5-fold, or more effect over a control. In embodiments, the therapeutically effective amount decreases bacterial burden detected in a tissue (in vitro or in vivo). For example, a therapeutically effective amount may show a decrease of at least 5%, 10%, 15%, 20%, 25%, 40%, 50%, 60%, 75%, 80%, 90%, 100% bacterial burden.

[0083] Dosages may be varied depending upon the requirements of the patient and the compound being employed. The dose administered to a patient, in the context of the present disclosure, should be sufficient to effect a beneficial therapeutic response in the patient over time. The size of the dose also will be determined by the existence, nature, and extent of any adverse side-effects. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treatment is initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under circumstances is reached. Dosage amounts and intervals can be adjusted individually to provide levels of the administered compound effective for the particular clinical indication being treated. This will provide a therapeutic regimen that is commensurate with the severity of the individual's disease state.

[0084] As used herein, the term "administering" means oral administration, administration as a suppository, topical contact, intravenous, parenteral, intraperitoneal, intramuscular, intralesional, intrathecal, intranasal or subcutaneous administration, or the implantation of a slow-release device, e.g., a mini-osmotic pump, to a subject. Administration is by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, e.g., intravenous, intramuscular, intra-arteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion,transdermal patches, etc. In embodiments, the administering does not include administration of any active agent other than the recited active agent.

[0085] “Patient”, “subject” or “subject in need thereof” refers to a living organism suffering from or prone to a disease or condition (e.g. an SA-associated disease or condition) or infection by a pathogen (e.g. staphylococcus aureus) that can be treated by administration of a composition as provided herein. Non-limiting examples include humans, other mammals, bovines, rats, mice, dogs, monkeys, goat, sheep, cows, deer, and other non-mammalian animals. In some embodiments, a patient is human. In embodiments, subject refers to an organism susceptible to infection by staphylococcus aureus. In embodiments, the organism susceptible to infection by staphylococcus aureus has eczema, a medical implant, or a chronic disease (e.g., diabetes, cancer, vascular disease, etc.). In embodiments, the organism susceptible to infection by staphylococcus aureus is in an intensive care unit of a hospital, has undergone surgery, has a medical implant or device, has a weakened immune system, or has an autoimmune disease.

[0086] The term “infection” or “infectious disease” refers to a disease or condition that can be caused by organisms such as a bacterium, virus, fungi or any other pathogenic microbial agents. In embodiments, the infectious disease is caused by staphycoloccus aureus. For example a staphylococcus aureus bacterium can infect a host cell or tissue and cause diseases. In embodiments, the infectious disease is a staphylococcus aureus (SA) associated disease. Non- limiting SA associated diseases include sepsis, pneumonia, and meningitis.

[0087] As used herein, the term "about” means a range of values including the specified value, which a person of ordinary skill in the art would consider reasonably similar to the specified value. In embodiments, about means within a standard deviation using measurements generally acceptable in the art. In embodiments, about means a range extending to + / - 10% of the specified value. In embodiments, about includes the specified value. VACCINE COMPOSITIONS

[0088] Provided herein, inter alia, are vaccine compositions capable of inducing an immune response against Staphylococcus aureus (SA). The vaccine compositions provided herein including embodiments thereof include a non-toxin SA antigen and an IL-17 activating adjuvant. Thus, in an aspect is provided a vaccine including a non-toxin Staphylococcus aureus (SA) antigen and an IL-17 activating adjuvant.

[0089] The term “immune response” used herein encompasses, but is not limited to, an “adaptive immune response”, also known as an “acquired immune response” in which adaptive immunity elicits immunological memory after an initial response to a specific pathogen or a specific type of cells that is targeted by the immune response, and leads to an enhanced response to that target on subsequent encounters. The induction of immunological memory can provide the basis of vaccination.

[0090] The term “immunogenic” or “antigenic” refers to a compound or composition that induces an immune response, e.g., cytotoxic T lymphocyte (CTL) response, a B cell response (for example, production of antibodies that specifically bind the epitope), an NK cell response or any combinations thereof, when administered to an immunocompetent subject. Thus, an immunogenic or antigenic composition is a composition capable of eliciting an immune response in an immunocompetent subject. For example, an immunogenic or antigenic composition can include one or more immunogenic epitopes associated with a pathogen or a specific type of cells that is targeted by the immune response. In addition, an immunogenic composition can include isolated nucleic acid constructs (such as DNA or RNA) that encode one or more immunogenic epitopes of the antigenic polypeptide that can be used to express the epitope(s) (and thus be used to elicit an immune response against this polypeptide or a related polypeptide associated with the targeted pathogen or type of cells).

[0091] The term “non-toxin Staphylococcus aureus antigen” or “non-toxin SA antigen” refers to a compound produced by staphylococcus aureus which does not damage the host cell or tissue by lysing the host cell or forming a pore within the cell membrane of the host cell. In embodiments, a non-toxin SA antigen does not directly cause symptoms of SA infection. In embodiments, a non-toxin SA antigen does not directly cause pathogenesis associated with SA infection. In embodiments, non-toxin SA antigens include molecules produced by SA that broadly increase the potential of SA to cause disease but do not directly cause symptoms associated with SA infection. For example, in embodiments, a non-toxin SA antigen enables the SA to infect a host cell. Thus, in embodiments, a non-toxin SA antigen includes an SA cell wall protein that enables the SA to bind to the host cell or tissue.

[0092] The term “vaccine” refers to a composition that can provide active acquired immunity to and / or therapeutic effect (e.g. treatment) of a particular disease or a pathogen. A vaccine typically contains one or more agents that can induce an immune response in a subject against a pathogen (e.g. staphylococcus aureus) or disease, i.e. a target pathogen or disease. Theimmunogenic agent stimulates the body’s immune system to recognize the agent as a threat or indication of the presence of the target pathogen or disease, thereby inducing immunological memory so that the immune system can more easily recognize and destroy any of the pathogen on subsequent exposure. Vaccines can be prophylactic (e.g. preventing or ameliorating the effects of a future infection by any natural or pathogen, or of an anticipated occurrence of infection in a predisposed subject) or therapeutic. The administration of vaccines is referred to as vaccination. In embodiments, a vaccine can provide an antigenic molecule (e.g. peptides) to a subject. The antigenic molecule delivered to the subject via the vaccine allows the subject to acquire immunity against the antigenic molecule. In the context of the vaccination against pathogenic infection, the vaccine composition can provide antigenic molecules that are associated with a certain pathogen, e.g. one or more peptides that are known to be expressed in the pathogen (e.g. staphylococcus aureus).

[0093] The term “adjuvant” or “vaccine adjuvant” or “pharmaceutically acceptable adjuvant” refer to compounds used in a vaccine to enhance (e.g., increase, accelerate, prolong, and / or target) the specific immune response to the vaccine in order to enhance the subject’s immune response to the vaccine. Adjuvants include aluminum salts, calcium salts, iron salts, zinc salts, acylated tyrosine, acylated sugars, cationically or anionically derivatized saccharides, polyphosphazenes, biodegradable microspheres, monophosphoryl lipid A, lipid A derivatives, 3- O-deacylated MPL, quil A, saponin, QS21, tocol, Freund's incomplete adjuvant, Adjuvant 65 (Merck and Company, Inc., Rahway, NJ), AS-2 (Glaxo-Smith-Kline, Philadelphia, PA), toll like receptor agonists (e.g., CpG ODNs), bioadhesives, mucoadhesives, microparticles, liposomes, polyoxyethylene ether formulations, polyoxyethylene ester formulations, muramyl peptides, imidazoquinolone compounds (e.g., imiquamod and its homologues), and the like. Human immunomodulators suitable for use as adjuvants include cytokines such as interleukins (e.g., IL- I, IL-2, IL-4, IL-5, IL-6, IL-7, IL-12, etc), macrophage colony stimulating factor, tumor necrosis factor, granulocyte, macrophage colony stimulating factor, and the like. In aspects, the adjuvant comprises a toll-like receptor agonist. In aspects, the adjuvant comprises an aluminum salt. In aspects, the adjuvant comprises a toll-like receptor agonist and an aluminum salt. In aspects, the adjuvant comprises an aluminum salt and monophosphoryl lipid A. In aspects, the adjuvant comprises squalene. In aspects, the adjuvant comprises monophosphoryl lipid A and QS-21. In aspects, the adjuvant comprises a toll-like receptor agonist, an aluminum salt, monophosphoryl lipid A, or a combination of two or more thereof.

[0094] The term “IL-17 activating adjuvant” refers to a molecule used in a vaccine provided herein that up-regulates or increases IL-17 expression, IL-17 activity, and / or IL-17 secretion from a cell (e.g. a T cell (e.g. a CD4+T cell)). As used herein, IL-17 refers to IL-17a or IL17b. Thus, the IL-17 activating adjuvant up-regulates or increases expression, activity, and / or secretion of IL-17a or IL-17b. In embodiments, an IL-17 activating adjuvant directly or indirectly increases expression of IL-17. In embodiments, an IL-17 activating adjuvant increases the biological activity of IL-17. For example, the IL-17 activating adjuvant may, in embodiments, increase binding of IL-17 to IL-17R. In embodiments, the IL-17 activating adjuvant increases IL-17 signaling. In embodiments, the IL-17 activating adjuvant increases IL- 17 signaling, thereby increasing the expression level or activity of one or more cytokines, including IL-6, G-CSF, GM-CSF, IL-1β, TGF-β, TNF-α or a combination thereof. In embodiments, the IL-17 activating adjuvant increases T cell activation. In embodiments, the IL- 17 activating adjuvant increases the level of CD4+T cells relative to the level of CD4+T cells in the absence of the IL-17 activating adjuvant. In embodiments, an IL-17 activating adjuvant increases the level of IL-17 secreted by a cell. For example, an IL-17 activating adjuvant may increase the amount of IL-17 released from a T cell (e.g. a CD4+T cell). Methods for detecting IL-17 expression are well-known in the art and include detecting IL-17 expression at the protein level or mRNA level. For example, in embodiments, IL-17 expression is detected by Western blot or Northern blot. In embodiments, IL-17 expression is detected by ELISA. In embodiments, IL-17 expression is detected by mass spectrometry. Methods for detecting IL-17 secretion from a cell are well-known in the art and include flow cytometric methods (e.g. ELISpot and flow cytometry), FACS, imaging methods. Methods of detecting CD4+T cells are well-known in the art and include antibody-based methods and flow cytometric methods.

[0095] As used herein, “IL-17” refers to IL-17a, IL-17b or a combination thereof. Therefore, in embodiments, IL-17 is refers to IL-17a. In embodiments, IL-17 refers to IL-17b. In embodiments, IL-17 refers to IL-17a and IL-17b.

[0096] The term “IL-17a protein” or “IL-17a” as used herein includes any of the recombinant or naturally-occurring forms of Interleukin-17A (IL-17a) protein, also known as cytotoxic T- lymphocyte-associated antigen 8, CTLA-8, or variants or homologs thereof that maintain IL-17a activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to IL-17a). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion ofthe sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring IL-17a protein. In embodiments, IL-17a is a primate IL-17a. In embodiments, IL-17a is human IL-17a. In embodiments, IL-17a is mouse IL-17a. In embodiment, IL-17a is rat IL-17a. In embodiments, the IL-17a protein is substantially identical to the protein identified by the UniProt reference number Q16552 or a variant or homolog having substantial identity thereto. In embodiments, the IL-17a protein is substantially identical to the protein identified by the UniProt reference number Q61453 or a variant or homolog having substantial identity thereto. In embodiments, the IL-17a protein is substantially identical to the protein identified by the UniProt reference number Q62386 or a variant or homolog having substantial identity thereto.

[0097] The term “IL-17b protein” or “IL-17b” as used herein includes any of the recombinant or naturally-occurring forms of Interleukin-17b (IL-17b) protein, also known as Cytokine Zcyto7, Interleukin-20 (IL-20), or variants or homologs thereof that maintain IL-17b activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to IL-17b). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring IL-17b protein. In embodiments, IL-17b is a primate IL-17b. In embodiments, IL-17b is human IL-17b. In embodiments, IL-17b is mouse IL-17b. In embodiment, IL-17b is rat IL- 17b. In embodiments, the IL-17b protein is substantially identical to the protein identified by the UniProt reference number Q9UHF5 or a variant or homolog having substantial identity thereto. In embodiments, the IL-17b protein is substantially identical to the protein identified by the UniProt reference number Q9QXT6 or a variant or homolog having substantial identity thereto.

[0098] In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 100% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 5% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 5% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 10% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression levelof IL-17 by at least 20% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 30% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 40% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 50% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 60% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 70% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 80% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 90% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 91% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 92% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 93% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 94% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 95% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 96% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 97% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 98% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression levelof IL-17 by at least 99% relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant.

[0099] In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500, 750 or 1000 - fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 1- fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 1.5 fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 2-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 2.5-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 3-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 4- fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 5- fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 6- fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 7- fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 8- fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 9- fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 10-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 20-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 30-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant.In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 40-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 50-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 60-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 70-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 80-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 90-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 100-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 250-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 500-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 750-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the expression level of IL-17 by at least 1000-fold relative to the expression level of IL-17 in the absence of the IL-17 activating adjuvant.

[0100] In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 100% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 5% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL- 17 activating adjuvant increases the activity of IL-17 by at least 5% relative to the activity of IL- 17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 10% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 20% relative to the activity of IL-17 in the absence ofthe IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 30% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 40% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 50% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 60% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 70% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 80% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 90% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 91% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 92% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 93% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 94% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 95% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 96% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 97% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 98% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 99% relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant.

[0101] In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500, 750 or 1000 -fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 1-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 1.5-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 2-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 2.5-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 3-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 4-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 5-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 6-fold relative to the activity of IL- 17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 7-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 8-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 9-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 10-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 20-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 30-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 40-fold relative to the activity of IL- 17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 50-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 60-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 70-fold relative to the activity of IL-17 in the absence of the IL-17activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 80-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 90-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 100-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 250-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 500-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 750-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the activity of IL-17 by at least 1000-fold relative to the activity of IL-17 in the absence of the IL-17 activating adjuvant.

[0102] In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell (e.g. a T cell) by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 100% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 5% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 5% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 10% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 20% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 30% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 40% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 50% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 60% relative to secretion of IL-17 from a cellin the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 70% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 80% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 90% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 91% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 92% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 93% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 94% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 95% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 96% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 97% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 98% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases secretion of IL-17 from a cell by at least 99% relative to secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant.

[0103] In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500, 750 or 1000 -fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 1-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL- 17 from a cell by at least 1.5-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases thesecretion of IL-17 from a cell by at least 2-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 2.5-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 3-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 4-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 5-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 6-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 7-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL- 17 from a cell by at least 8-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 9-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 10-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 20-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 30-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 40-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 50-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 60-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 70-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL- 17 from a cell by at least 80-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 90-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 100-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 250-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 500-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 750-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant. In embodiments, the IL-17 activating adjuvant increases the secretion of IL-17 from a cell by at least 1000-fold relative to the secretion of IL-17 from a cell in the absence of the IL-17 activating adjuvant.

[0104] In embodiments, the IL-17 activating adjuvant activates IFN-γ. For example, in embodiments, the IL-17 activating adjuvant up-regulates or increases IFN-γ expression, IFN-γ activity, and / or IFN-γ secretion from a cell (e.g. a T cell (e.g. a CD4+T cell)). In embodiments, an IL-17 activating adjuvant directly or indirectly increases expression of IFN-γ. In embodiments, an IL-17 activating adjuvant increases the biological activity of IFN-γ. For example, the IL-17 activating adjuvant may, in embodiments, increase IFN-γ signaling. In embodiments, the IL-17 activating adjuvant increases IFN-γ signaling pathways in macrophages, B cells, and CD8+ cytotoxic T cells. In embodiments, an IL-17 activating adjuvant increases the level of IFN-γ secreted by a cell. For example, an IL-17 activating adjuvant may increase the amount of IFN-γ released from a T cell (e.g. a CD4+T cell). Methods for detecting IFN-γ expression are well-known in the art and include detecting IFN-γ expression at the protein level or mRNA level. For example, in embodiments, IFN-γ expression is detected by Western blot or Northern blot. In embodiments, IFN-γ expression is detected by ELISA. In embodiments, IFN-γ expression is detected by mass spectrometry. Methods for detecting IFN-γ secretion from a cell are well-known in the art and include flow cytometric methods and antibody based methods.

[0105] The term “IFN-γ protein” or “IFN-γ” as used herein includes any of the recombinant or naturally-occurring forms of interferon-γ (IFN-γ) protein, also known as interferon-gamma, IFN- gamma, or variants or homologs thereof that maintain IFN-γ activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to IFN-γ). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring IFN-γ protein. In embodiments, IFN-γ is a primate IFN-γ. In embodiments, IFN-γ is human IFN-γ. In embodiments, IFN-γ is mouse IFN-γ. In embodiment, IFN-γ is rat IFN-γ. In embodiments, the IFN-γ protein is substantially identical to the protein identified by the UniProt reference number P01579 or a variant or homolog having substantial identity thereto. In embodiments, the IFN-γ protein is substantially identical to the protein identified by the UniProt reference number P01579 or a variant or homolog having substantial identity thereto.

[0106] In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 100% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 5% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 5% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 10% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 20% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 30% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 40% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 50% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 60% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression levelof IFN-γ by at least 70% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 80% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 90% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 91% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 92% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 93% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 94% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 95% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 96% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 97% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 98% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 99% relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant.

[0107] In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500, 750 or 1000 - fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 1- fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 1.5-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 2-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant..In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 2.5-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 3-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 4- fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 5- fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 6- fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 7- fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 8- fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 9- fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 10-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 20-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 30-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 40-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 50-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 60-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 70-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 80-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least90-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 100-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 250-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 500-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 750-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the expression level of IFN-γ by at least 1000-fold relative to the expression level of IFN-γ in the absence of the IFN-γ activating adjuvant.

[0108] In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 100% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 5% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 5% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 10% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 20% relative to the activity of IFN- γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 30% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 40% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN- γ by at least 50% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 60% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 70% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 80% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 90% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 91% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN- γ by at least 92% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 93% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 94% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 95% relative to the activity of IFN- γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 96% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 97% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN- γ by at least 98% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 99% relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant.

[0109] In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500, 750 or 1000 -fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 1-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 1.5-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 2-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 2.5-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 3-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN- γ by at least 4-fold relative to the activity of IFN-γ in the absence of the IFN-γ activatingadjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 5-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 6-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 7-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 8-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 9-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 10-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 20-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN- γ by at least 30-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 40-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 50-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 60-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 70-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 80-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 90-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 100-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN- γ by at least 250-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 500-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 750-foldrelative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the activity of IFN-γ by at least 1000-fold relative to the activity of IFN-γ in the absence of the IFN-γ activating adjuvant.

[0110] In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell (e.g. a T cell) by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 100% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 5% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 5% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 10% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 20% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 30% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 40% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 50% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 60% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 70% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 80% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 90% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 91% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 92% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvantincreases secretion of IFN-γ from a cell by at least 93% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 94% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 95% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 96% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 97% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 98% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases secretion of IFN-γ from a cell by at least 99% relative to secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant.

[0111] In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500, 750 or 1000 -fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 1-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 1.5-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 2-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 2.5-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 3-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 4-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 5-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by atleast 6-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 7-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 8-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 9-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 10-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 20-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 30-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 40-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 50-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 60-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 70-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 80-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 90-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 100-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 250-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 500-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. Inembodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 750-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant. In embodiments, the IFN-γ activating adjuvant increases the secretion of IFN-γ from a cell by at least 1000-fold relative to the secretion of IFN-γ from a cell in the absence of the IFN-γ activating adjuvant.

[0112] For the vaccine provided herein, in embodiments, the non-toxin SA antigen may be derived from a protein expressed on the cell wall of a SA, anchored to the cell wall of SA, or associated with the cell wall of SA. In embodiments, the non-toxin SA antigen is a cell surface non-toxin SA antigen. As used herein, a “cell surface non-toxin SA antigen” refers to a non-toxin SA antigen that in natural state is expressed on the surface of an SA or is associated with the SA cell wall. Thus, in embodiments, the non-toxin SA antigen is in its natural state expressed on the surface of an SA bacteria. In embodiments, the non-toxin SA antigen is in its natural state associated with the cell wall of an SA bacteria. For example, the non-toxin SA antigen may be non-covalently or covalently bound to the cell wall of the SA bacteria. In embodiments, the non- toxin SA antigen may be derived from a non-toxin SA antigen expressed on the cell of an SA bacteria. In embodiments, a non-toxin SA antigen may be bound to the SA cell wall by covalent attachment of the non-toxin SA antigen to an SA cell wall component. For example, in embodiments, an amino acid side chain of the non-toxin SA antigen may be covalently attached to a peptidoglycan of the SA cell wall. In embodiments, the non-toxin SA antigen may be a cell wall protein associated with inhibiting opsonophagocytic clearance of the SA. In embodiments, the non-toxin SA antigen may be a cell wall protein associated with adhesion of the SA to a host cell or tissue. In embodiments, the non-toxin SA antigen may be a cell wall protein associated with inhibiting or decreasing the host’s immune response.

[0113] In embodiments, the non-toxin SA antigen is a recombinant SA protein.

[0114] In embodiments, the non-toxin SA antigen is covalently attached to the IL-17 activating adjuvant. In embodiments, the non-toxin SA antigen is covalently attached to the IL-17 activating adjuvant by a peptide linker. For example, the IL-17 activating adjuvant may be covalently attached to the N-terminus or C-terminus of a non-toxin SA antigen. In embodiments, the peptide linker has a length of about 1 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 2 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 4 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 6 to about 50 amino acids residues. In embodiments, thepeptide linker has a length of about 8 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 10 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 12 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 14 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 16 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 18 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 20 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 22 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 24 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 26 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 28 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 30 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 32 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 34 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 36 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 38 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 40 to about 50 amino acids in length. In embodiments, the peptide linker has a length of about 42 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 44 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 46 to about 50 amino acids residues. In embodiments, the peptide linker has a length of about 48 to about 50 amino acids residues.

[0115] In embodiments, the peptide linker has a length of about 1 to about 48 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 46 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 44 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 42 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 40 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 38 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 36 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 34 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 32 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 30 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 28 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 26 amino acidsresidues. In embodiments, the peptide linker has a length of about 1 to about 24 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 22 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 20 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 18 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 16 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 14 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 12 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 10 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 8 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 6 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 4 amino acids residues. In embodiments, the peptide linker has a length of about 1 to about 2 amino acids residues. In embodiments, the peptide linker has a length of about 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or 50 residues. In embodiments, the peptide linker includes the sequence of SEQ ID NO:3. In embodiments, the peptide linker is the sequence of SEQ ID NO:3. In embodiments, the peptide linker includes the sequence of SEQ ID NO:4. In embodiments, the peptide linker is the sequence of SEQ ID NO:4. In embodiments, the peptide linker includes the sequence of SEQ ID NO:7. In embodiments, the peptide linker is the sequence of SEQ ID NO:7. Suitable linkers for covalently attaching the IL-17 activating adjuvant to the SA antigen are well-known in the art, and are described in more detail in Chen X, Zaro JL, Shen WC. Fusion protein linkers: property, design and functionality. Adv Drug Deliv Rev.2013 Oct;65(10):1357-69. doi: 10.1016 / j.addr.2012.09.039. Epub 2012 Sep 29. PMID: 23026637; PMCID: PMC3726540., which is incorporated herein in its entirety and for all purposes.

[0116] In embodiments, the non-toxin SA antigen is iron-regulated surface determinant B (IsdB), iron-regulated surface determinant A (IsdA), manganese transport protein C (mntC), hydroxamate siderophore binding lipoprotein (FhuD2), serine-aspartate repeat protein E (sdrE), protein A (SpA), clumping factor A (clfA), Ess-secreted protein A (EsxA), Ess-secreted protein B (EsxB), clumping factor B (clfB), serine aspartate repeat protein D (SdrD), fibronectin binding protein A (FnBPA), fibronectin binding protein B (FnBPB), surface protein G (SasG), 5′- nucleotidase adenosine synthase A, surface protein X (SasX), surface protein C (SasC), coagulase, capsular polysaccharide 5 (CP5), capsular polysaccharide 8 (CP8), aureolysin (Aur), whole inactivated SA, Csa1, wall teichoic acid, lipoteichoic acid, glucosaminidase (Gmd),Staphylococcal binder of immunoglobulin (Sbi), extracellular fibrinogen-binding protein (Efb), nuclease (Nuc), extracellular adherence protein (Eap), serine-aspartate repeat-containing protein E (SdrE), serine-aspartate repeat-containing protein C (SdrC), collagen binding protein (Cna), or a combination thereof. In embodiments, the non-toxin SA antigen is IsdB. In embodiments, the non-toxin SA antigen is IsdA. In embodiments, the non-toxin SA antigen is mntC. In embodiments, the non-toxin SA antigen is FhuD2. In embodiments, the non-toxin SA antigen is sdrE. In embodiments, the non-toxin SA antigen is SpA. In embodiments, the non-toxin SA antigen is clfA. In embodiments, the non-toxin SA antigen is EsxA. In embodiments, the non- toxin SA antigen is EsxB. In embodiments, the non-toxin SA antigen is clfB. In embodiments, the non-toxin SA antigen is SdrD. In embodiments, the non-toxin SA antigen is FnBPA. In embodiments, the non-toxin SA antigen is FnBPB. In embodiments, the non-toxin SA antigen is SasG. In embodiments, the non-toxin SA antigen is 5′-nucleotidase adenosine synthase A. In embodiments, the non-toxin SA antigen is SasX. In embodiments, the non-toxin SA antigen is SasC. In embodiments, the non-toxin SA antigen is coagulase. In embodiments, the non-toxin SA antigen is CP5. In embodiments, the non-toxin SA antigen is CP8. In embodiments, the non- toxin SA antigen is Aur. In embodiments, the non-toxin SA antigen is whole inactivated SA. In embodiments, the non-toxin SA antigen is Csa1. In embodiments, the non-toxin SA antigen is wall teichoic acid. In embodiments, the non-toxin SA antigen is lipoteichoic acid. In embodiments, the non-toxin SA antigen is Gmd. In embodiments, the non-toxin SA antigen is Sbi. In embodiments, the non-toxin SA antigen is Efb. In embodiments, the non-toxin SA antigen is Nuc. In embodiments, the non-toxin SA antigen is Eap. In embodiments, the non-toxin SA antigen is SdrE. In embodiments, the non-toxin SA antigen is SdrC. In embodiments, the non-toxin SA antigen is Cna.

[0117] In embodiments, the non-toxin SA antigen is IsdB, IsdA, mntC, FhuD2, sdrE, SpA, clfA, EsxA, EsxB, or a combination thereof. In embodiments, the non-toxin SA antigen is IsdB. In embodiments, the non-toxin SA antigen is IsdA. In embodiments, the non-toxin SA antigen is mntC. In embodiments, the non-toxin SA antigen is FhuD2. In embodiments, the non-toxin SA antigen is sdrE. In embodiments, the non-toxin SA antigen is SpA. In embodiments, the non- toxin SA antigen is clfA. In embodiments, the non-toxin SA antigen is EsxA. In embodiments, the non-toxin SA antigen is EsxB.

[0118] The term “IsdB protein” or “IsdB” as used herein includes any of the recombinant or naturally-occurring forms of iron-regulated surface determinant B (IsdB) protein, also knownFur-regulated protein B, or variants or homologs thereof that maintain IsdB activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to IsdB). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring IsdB protein. In embodiments, the IsdB protein is substantially identical to the protein identified by the UniProt reference number Q7A656 or a variant or homolog having substantial identity thereto. In embodiments, the IsdB protein is substantially identical to the protein identified by the UniProt reference number Q2FZF0 or a variant or homolog having substantial identity thereto. In embodiments, the IsdB protein is substantially identical to the protein identified by the UniProt reference number Q2FHV2 or a variant or homolog having substantial identity thereto. In embodiments, the IsdB protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 90% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 91% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 92% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 93% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 94% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 95% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 96% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 97% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 98% identity to SEQ ID NO:11. In embodiments, the IsdB protein includes a sequence having at least 99% identity to SEQ ID NO:11. In embodiments, said IsdB protein includes SEQ ID NO:11. In embodiments, said IsdB protein is SEQ ID NO:11.

[0119] The term “IsdA protein” or “IsdA” as used herein includes any of the recombinant or naturally-occurring forms of iron-regulated surface determinant A (IsdA) protein, also known Fur-regulated protein A, staphylococcal transferrin-binding protein A or variants or homologs thereof that maintain IsdA activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to IsdA). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring IsdA protein. In embodiments, the IsdA protein issubstantially identical to the protein identified by the UniProt reference number A6QG31 or a variant or homolog having substantial identity thereto. In embodiments, the IsdA protein is substantially identical to the protein identified by the UniProt reference number Q2FHV1 or a variant or homolog having substantial identity thereto. In embodiments, the IsdA protein is substantially identical to the protein identified by the UniProt reference number P0C1S5 or a variant or homolog having substantial identity thereto. In embodiments, the IsdA protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 90% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 91% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 92% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 93% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 94% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 95% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 96% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 97% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 98% identity to SEQ ID NO:9. In embodiments, the IsdA protein includes a sequence having at least 99% identity to SEQ ID NO:9. In embodiments, said IsdA protein includes SEQ ID NO:9. In embodiments, said IsdA protein is SEQ ID NO:9.

[0120] The term “mntC protein” or “mntC” as used herein includes any of the recombinant or naturally-occurring forms of manganese transport protein C (mntC) protein, or variants or homologs thereof that maintain mntC activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to mntC). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring mntC protein. In embodiments, the mntC protein is substantially identical to the protein identified by the UniProt reference number Q8VQS9 or a variant or homolog having substantial identity thereto. In embodiments, the mntC protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequence having at least 90% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequence having at least 91% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequencehaving at least 92% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequence having at least 93% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequence having at least 94% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequence having at least 95% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequence having at least 96% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequence having at least 97% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequence having at least 98% identity to SEQ ID NO:8. In embodiments, the mntC protein includes a sequence having at least 99% identity to SEQ ID NO:8. In embodiments, said mntC protein includes SEQ ID NO:8. In embodiments, said mntC protein is SEQ ID NO:8.

[0121] The term “FhuD2 protein” or “FhuD2” as used herein includes any of the recombinant or naturally-occurring forms of hydroxamate siderophore binding lipoprotein (FhuD2) protein, or variants or homologs thereof that maintain FhuD2 activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to FhuD2). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring FhuD2 protein. In embodiments, the FhuD2 protein is substantially identical to the protein identified by the UniProt reference number A0A0H3JRD4 or a variant or homolog having substantial identity thereto. In embodiments, the FhuD2 protein is substantially identical to the protein identified by the UniProt reference number A0A0H3K1A0 or a variant or homolog having substantial identity thereto. In embodiments, the FhuD2 protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:12. In embodiments, the FhuD2 protein includes a sequence having at least 90% identity to SEQ ID NO:12. In embodiments, the FhuD2 protein includes a sequence having at least 91% identity to SEQ ID NO:12. In embodiments, the FhuD2 protein includes a sequence having at least 92% identity to SEQ ID NO:12. In embodiments, the FhuD2 protein includes a sequence having at least 93% identity to SEQ ID NO:12. In embodiments, the FhuD2 protein includes a sequence having at least 94% identity to SEQ ID NO:12. In embodiments, the FhuD2 protein includes a sequence having at least 95% identity to SEQ ID NO:12. In embodiments, the FhuD2 protein includes a sequence having at least 96% identity to SEQ ID NO:12. In embodiments, the FhuD2 protein includes a sequence having at least 97% identity to SEQ ID NO:12. In embodiments, the FhuD2 protein includes a sequence having at least 98% identity to SEQ ID NO:12. In embodiments, the FhuD2protein includes a sequence having at least 99% identity to SEQ ID NO:12. In embodiments, said FhuD2 protein includes SEQ ID NO:12. In embodiments, said FhuD2 protein is SEQ ID NO:12.

[0122] The term “sdrE protein” or “sdrE” as used herein includes any of the recombinant or naturally-occurring forms of serine-aspartate repeat protein E (sdrE) protein, or variants or homologs thereof that maintain sdrE activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to sdrE). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring sdrE protein. In embodiments, the sdrE protein is substantially identical to the protein identified by the UniProt reference number O86489 or a variant or homolog having substantial identity thereto. In embodiments, the sdrE protein is substantially identical to the protein identified by the UniProt reference number Q932F7 or a variant or homolog having substantial identity thereto. In embodiments, the sdrE protein is substantially identical to the protein identified by the UniProt reference number Q99W46 or a variant or homolog having substantial identity thereto. In embodiments, the sdrE protein is substantially identical to the protein identified by the UniProt reference number Q2FJ77 or a variant or homolog having substantial identity thereto. In embodiments, the SdrE protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 90% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 91% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 92% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 93% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 94% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 95% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 96% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 97% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 98% identity to SEQ ID NO:10. In embodiments, the SdrE protein includes a sequence having at least 99% identity to SEQ ID NO:10. In embodiments, said SdrE protein includes SEQ ID NO:10. In embodiments, said SdrE protein is SEQ ID NO:10.

[0123] The term “SpA protein” or “SpA” as used herein includes any of the recombinant or naturally-occurring forms of protein A (SpA) protein, also known as immunoglobulin G-binding protein A, IgG-binding protein A or variants or homologs thereof that maintain SpA activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to SpA). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring SpA protein. In embodiments, the SpA protein is substantially identical to the protein identified by the UniProt reference number P02976 or a variant or homolog having substantial identity thereto. In embodiments, the SpA protein is substantially identical to the protein identified by the UniProt reference number P38507 or a variant or homolog having substantial identity thereto. In embodiments, the SpA protein is substantially identical to the protein identified by the UniProt reference number P99134 or a variant or homolog having substantial identity thereto.

[0124] The term “clfA protein” or “clfA” as used herein includes any of the recombinant or naturally-occurring forms of clumping factor A (clfA) protein, also known as fibrinogen receptor A, fibrinogen-binding protein A or variants or homologs thereof that maintain clfA activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to clfA). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring clfA protein. In embodiments, the clfA protein is substantially identical to the protein identified by the UniProt reference number Q53653 or a variant or homolog having substantial identity thereto. In embodiments, the clfA protein is substantially identical to the protein identified by the UniProt reference number Q6GIK4 or a variant or homolog having substantial identity thereto.

[0125] The term “EsxAB protein” or “EsxAB” as used herein includes any of the recombinant or naturally-occurring forms of Type VII secretion system extracellular protein AB (EsxAB) protein, also known as Type VII secretion system extracellular protein A, Type VII secretion system extracellular protein B, or variants or homologs thereof that maintain EsxAB activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to EsxAB). In embodiments, EsxAB protein refers to a single subunit or both subunits of EsxAB. In embodiments, EsxAB refers to EsxA, EsxB, or a combination thereof. In embodiments, EsxAB refers to EsxA. In embodiments, EsxAB refers to EsxB. In some aspects, the variants orhomologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring EsxAB protein. In embodiments, the EsxAB protein is substantially identical to the protein identified by the UniProt reference number A0A0H2XIE9 or a variant or homolog having substantial identity thereto. In embodiments, the EsxAB protein is substantially identical to the protein identified by the UniProt reference number A0A0H2XI99 or a variant or homolog having substantial identity thereto.

[0126] In embodiments, the EsxA protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 90% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 91% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 92% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 93% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 94% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 95% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 96% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 97% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 98% identity to SEQ ID NO:16. In embodiments, the EsxA protein includes a sequence having at least 99% identity to SEQ ID NO:16. In embodiments, said EsxA protein includes SEQ ID NO:16. In embodiments, said EsxA protein is SEQ ID NO:16.

[0127] In embodiments, the EsxB protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes a sequence having at least 90% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes a sequence having at least 91% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes a sequence having at least 92% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes a sequence having at least 93% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes a sequence having at least 94% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes a sequence having at least 95% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes a sequence having at least 96% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes a sequence having at least 97% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes asequence having at least 98% identity to SEQ ID NO:17. In embodiments, the EsxB protein includes a sequence having at least 99% identity to SEQ ID NO:17. In embodiments, said EsxB protein includes SEQ ID NO:17. In embodiments, said EsxB protein is SEQ ID NO:17.

[0128] The term “clfB protein” or “clfB” as used herein includes any of the recombinant or naturally-occurring forms of clumping factor B (clfB) protein, also known as Fibrinogen receptor B, Fibrinogen-binding protein B or variants or homologs thereof that maintain clfB activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to clfB). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring clfB protein. In embodiments, the clfB protein is substantially identical to the protein identified by the UniProt reference number O86476 or a variant or homolog having substantial identity thereto. In embodiments, the clfB protein is substantially identical to the protein identified by the UniProt reference number Q6GDH2 or a variant or homolog having substantial identity thereto. In embodiments, the clfB protein is substantially identical to the protein identified by the UniProt reference number Q7A382 or a variant or homolog having substantial identity thereto.

[0129] The term “SdrD protein” or “SdrD” as used herein includes any of the recombinant or naturally-occurring forms of serine aspartate repeat protein D (SdrD) protein, or variants or homologs thereof that maintain SdrD activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to SdrD). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring SdrD protein. In embodiments, the SdrD protein is substantially identical to the protein identified by the UniProt reference number Q2G0L4 or a variant or homolog having substantial identity thereto. In embodiments, the SdrD protein is substantially identical to the protein identified by the UniProt reference number Q2FJ78 or a variant or homolog having substantial identity thereto. In embodiments, the SdrD protein is substantially identical to the protein identified by the UniProt reference number Q8NXX6 or a variant or homolog having substantial identity thereto.

[0130] The term “FnBPA protein” or “FnBPA” as used herein includes any of the recombinant or naturally-occurring forms of fibronectin binding protein A (FnBPA) protein, or variants or homologs thereof that maintain FnBPA activity (e.g. within at least 50%, 80%, 90%, 95%, 96%,97%, 98%, 99% or 100% activity compared to FnBPA). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring FnBPA protein. In embodiments, the FnBPA protein is substantially identical to the protein identified by the UniProt reference number P14738 or a variant or homolog having substantial identity thereto. In embodiments, the FnBPA protein is substantially identical to the protein identified by the UniProt reference number G4XGY3or a variant or homolog having substantial identity thereto.

[0131] The term “FnBPB protein” or “FnBPB” as used herein includes any of the recombinant or naturally-occurring forms of fibronectin binding protein B (FnBPB) protein, or variants or homologs thereof that maintain FnBPB activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to FnBPB). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring FnBPB protein. In embodiments, the FnBPB protein is substantially identical to the protein identified by the UniProt reference number A0A0H2XKG3 or a variant or homolog having substantial identity thereto.

[0132] The term “SasG protein” or “SasG” as used herein includes any of the recombinant or naturally-occurring forms of surface protein G (SasG) protein, or variants or homologs thereof that maintain SasG activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to SasG). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring SasG protein. In embodiments, the SasG protein is substantially identical to the protein identified by the UniProt reference number Q2G2B2 or a variant or homolog having substantial identity thereto. In embodiments, the SasG protein is substantially identical to the protein identified by the UniProt reference number A0A2Z6G142 or a variant or homolog having substantial identity thereto.

[0133] The term “5′-nucleotidase adenosine synthase A protein” or “5′-nucleotidase adenosine synthase A” as used herein includes any of the recombinant or naturally-occurring forms of 5′- nucleotidase adenosine synthase A protein, also known as 5'-nucleotidase, LPXTG-anchored adenosine synthase AdsA, adsA or variants or homologs thereof that maintain 5′-nucleotidaseadenosine synthase A activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to 5′-nucleotidase adenosine synthase A). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring 5′-nucleotidase adenosine synthase A protein. In embodiments, the 5′-nucleotidase adenosine synthase A protein is substantially identical to the protein identified by the UniProt reference number A0A1S6DAJ0 or a variant or homolog having substantial identity thereto. In embodiments, the 5′-nucleotidase adenosine synthase A protein is substantially identical to the protein identified by the UniProt reference number A0A9Q4YSH9 or a variant or homolog having substantial identity thereto.

[0134] The term “SasX protein” or “SasX” as used herein includes any of the recombinant or naturally-occurring forms of surface protein X (SasX) protein, or variants or homologs thereof that maintain SasX activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to SasX). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring SasX protein. In embodiments, the SasX protein is substantially identical to the protein identified by the UniProt reference number A0A3S9JKX6 or a variant or homolog having substantial identity thereto. In embodiments, the SasX protein is substantially identical to the protein identified by the UniProt reference number A0A346D9R1 or a variant or homolog having substantial identity thereto. In embodiments, the SasX protein is substantially identical to the protein identified by the UniProt reference number A0A1L7H885 or a variant or homolog having substantial identity thereto.

[0135] The term “SasC protein” or “SasC” as used herein includes any of the recombinant or naturally-occurring forms of surface protein C (SasC) protein, also known as Surface antigen SasC, LPXTG-anchored repetitive surface protein SasC, or variants or homologs thereof that maintain SasC activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to SasC). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring SasC protein. In embodiments, the SasC protein is substantially identical to the protein identified by the UniProt reference number C7BUR8 or a variant or homologhaving substantial identity thereto. In embodiments, the SasC protein is substantially identical to the protein identified by the UniProt reference number A0A898CMB5 or a variant or homolog having substantial identity thereto. In embodiments, the SasC protein is substantially identical to the protein identified by the UniProt reference number A0A6B0CEM1 or a variant or homolog having substantial identity thereto.

[0136] The term “coagulase protein” or “coagulase” as used herein includes any of the recombinant or naturally-occurring forms of coagulase protein, or variants or homologs thereof that maintain coagulase activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to coagulase). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring coagulase protein. In embodiments, the coagulase protein is substantially identical to the protein identified by the UniProt reference number Q53655 or a variant or homolog having substantial identity thereto. In embodiments, the coagulase protein is substantially identical to the protein identified by the UniProt reference number Q9KW81 or a variant or homolog having substantial identity thereto.

[0137] “Capsular polysaccharide type 5” or “CP5” refers to a polysaccharide on the cell wall of SA, where the polysaccharide includes repeating units of two molecules of 2-acetamido-2- deoxy-fucose, wherein 2-acetamido-2-deoxy-fucose includes one D-fucose monomer and one L- fucose monomer, and one molecule of 2-acetamido-2-deoxy-mannose, with the sugars linked together via glycosidic bonds. For example, CP5 includes repeating units of D-FucNAc-L- FucNAc-ManNAc, where "FucNAc" refers to N-acetyl-fucose and "ManNAc" refers to N- acetyl-mannosamine. In embodiments, CP5 is associated with SA’s function of evading the host’s immune response by inhibiting phagocytosis.

[0138] “Capsular polysaccharide 8” or “CP8” refers to a polysaccharide on the cell wall of SA, where the polysaccharide includes repeating units of alternating beta-N-acetylmannosaminuronic acid (ManNAcA) and alpha-fucosamine (FucNAc). In embodiments, the ManNAcA units are O- acetylated at the 4-position. The sugar monomers of CP8 are attached via beta-1,3 glycosidic bonds.

[0139] The term “Aur protein” or “Aur” as used herein includes any of the recombinant or naturally-occurring forms of aureolysin (Aur), also known as Zinc metalloproteinase aureolysin, Staphylococcus aureus neutral proteinase, or variants or homologs thereof that maintain Auractivity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to Aur). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring Aur protein. In embodiments, the Aur protein is substantially identical to the protein identified by the UniProt reference number P81177 or a variant or homolog having substantial identity thereto.

[0140] The term “Csa1 protein” or “Csa1” as used herein includes any of the recombinant or naturally-occurring forms of Csa1 family protein (Csa1), or variants or homologs thereof that maintain Csa1 activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to Csa1). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring Csa1 protein. In embodiments, the Csa1protein is substantially identical to the protein identified by the UniProt reference number A0A517JRH5 or a variant or homolog having substantial identity thereto.

[0141] “Wall teichoic acid” or “WTA” refers to a polymer on the cell wall of staphylococcus aureus associated with bacterial virulence and host interaction. WTA includes chains of repeating ribitol phosphate units. In embodiments, the ribitol phosphate units are substituted with D-alanine, N-acetylglucosamine (GlcNAc), or a combination thereof.

[0142] “Lipoteichoic acid” or “LTA” refers to an anionic polymer including repeating units of 1,3-linked glycerol phosphate. LTA is typically anchored to the SA cell wall by a glycolipid, and is associated with maintaining cell wall integrity and SA pathogenicity.

[0143] The term “Gmd protein” or “Gmd” as used herein includes any of the recombinant or naturally-occurring forms of glucosaminidase (Gmd) protein, also known as bifunctional autolysin, Mannosyl-glycoprotein endo-beta-N-acetylglucosaminidase or variants or homologs thereof that maintain Gmd activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to Gmd). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring Gmd protein. In embodiments, the Gmd protein issubstantially identical to the protein identified by the UniProt reference number P0C5Z8 or a variant or homolog having substantial identity thereto.

[0144] The term “Sbi protein” or “Sbi” as used herein includes any of the recombinant or naturally-occurring forms of Staphylococcal binder of immunoglobulin (Sbi) protein, also known as Immunoglobulin-binding protein Sbi, or variants or homologs thereof that maintain Sbi activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to Sbi). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring Sbi protein. In embodiments, the Sbi protein is substantially identical to the protein identified by the UniProt reference number A6QJQ7 or a variant or homolog having substantial identity thereto. In embodiments, the Sbi protein is substantially identical to the protein identified by the UniProt reference number Q2FE79 or a variant or homolog having substantial identity thereto.

[0145] The term “Efb protein” or “Efb” as used herein includes any of the recombinant or naturally-occurring forms of extracellular fibrinogen-binding protein (Efb) protein, also known as fibrinogen-binding protein, or variants or homologs thereof that maintain Efb activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to Efb). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring Efb protein. In embodiments, the Efb protein is substantially identical to the protein identified by the UniProt reference number A6QG59 or a variant or homolog having substantial identity thereto. In embodiments, the Efb protein is substantially identical to the protein identified by the UniProt reference number A0A0H2XIH9 or a variant or homolog having substantial identity thereto. In embodiments, the Efb protein is substantially identical to the protein identified by the UniProt reference number P0C6P2 or a variant or homolog having substantial identity thereto.

[0146] The term “Nuc protein” or “Nuc” as used herein includes any of the recombinant or naturally-occurring forms of nuclease (Nuc) protein, also known as thermonuclease, or variants or homologs thereof that maintain Nuc activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to Nuc). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across thewhole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring Nuc protein. In embodiments, the Nuc protein is substantially identical to the protein identified by the UniProt reference number P00644 or a variant or homolog having substantial identity thereto.

[0147] The term “Eap protein” or “Eap” as used herein includes any of the recombinant or naturally-occurring forms of extracellular adherence protein (Eap) protein, or variants or homologs thereof that maintain Eap activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to Eap). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring Eap protein. In embodiments, the Eap protein is substantially identical to the protein identified by the UniProt reference number A0A5P9NYM0 or a variant or homolog having substantial identity thereto. In embodiments, the Eap protein is substantially identical to the protein identified by the UniProt reference number A0AAE2ZZL2 or a variant or homolog having substantial identity thereto.

[0148] The term “SdrE protein” or “SdrE” as used herein includes any of the recombinant or naturally-occurring forms of serine-aspartate repeat-containing protein E (SdrE) protein, or variants or homologs thereof that maintain SdrE activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to SdrE). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring SdrE protein. In embodiments, the SdrE protein is substantially identical to the protein identified by the UniProt reference number O86489 or a variant or homolog having substantial identity thereto. In embodiments, the SdrE protein is substantially identical to the protein identified by the UniProt reference number Q2FJ77 or a variant or homolog having substantial identity thereto.

[0149] The term “SdrC protein” or “SdrC” as used herein includes any of the recombinant or naturally-occurring forms of serine-aspartate repeat-containing protein C (SdrC) protein, or variants or homologs thereof that maintain SdrC activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to SdrC). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200continuous amino acid portion) compared to a naturally occurring SdrC protein. In embodiments, the SdrC protein is substantially identical to the protein identified by the UniProt reference number O86489 or a variant or homolog having substantial identity thereto. In embodiments, the SdrC protein is substantially identical to the protein identified by the UniProt reference number Q2FJ79 or a variant or homolog having substantial identity thereto.

[0150] “Whole inactivated SA” refers to a staphylococcus aureus cell exposed to heat, inactivating compounds (e.g. formaldehyde, beta-propiolactone), or radiation so that the SA is unable to replicate but is capable of inducing an immune response when administered to a subject.

[0151] For the vaccine provided herein, in embodiments, the non-toxin SA antigen is a fragment or a portion of a non-toxin SA antigen. For example, in embodiments, the non-toxin SA antigen includes a fragment or a portion of a non-toxin SA protein or non-toxin SA lipoprotein. In embodiments, the non-toxin SA antigen is a fragment or a portion of a non-toxin SA antigen that induces production of a neutralizing antibody. For example, the fragment or portion of a non-toxin SA may induce production of an antibody that binds an epitope that inhibits the function of the non-toxin SA antigen.

[0152] For the vaccine provided herein, in embodiments, the non-toxin SA antigen includes a combination of two or more non-toxin SA antigens provided herein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 2, 3, 4, 5, 6, 7, 8, 9 or 10 non-toxin SA antigens provided herein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 2 non-toxin SA antigens provided herein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 3 non-toxin SA antigens provided herein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 4 non-toxin SA antigens provided herein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 5 non-toxin SA antigens provided herein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 6 non-toxin SA antigens provided herein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 7 non-toxin SA antigens provided herein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 8 non-toxin SA antigens provided herein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 9 non-toxin SA antigens providedherein including embodiments thereof. In embodiments, the non-toxin SA antigen is a combination of 10 non-toxin SA antigens provided herein including embodiments thereof.

[0153] In embodiments, the vaccine further includes a toxin SA antigen. As used herein, the term “toxin SA antigen” refers to a molecule produced by Staphylococcus aureus that binds to the host cell membrane thereby forming a pore in the host cell membrane (e.g. Hla, LukED), lysing the host cell (e.g. phenol soluble modulin), inducing host cell cytotoxicity, or inducing a proinflammatory response the host cell (e.g. TSST, phenol soluble modulin). For example, in embodiments, a toxin SA antigen is a cytotoxic compound that causes cell death of an infected cell or surrounding cells. The toxin SA antigen may be a subunit (e.g. LukS–PV, LukF–PV, etc.) or component of a complex that when assembled causes damage to a host cell or tissue. In embodiments, a toxin SA antigen when unbound to its counterpart does not cause damage to the host cell or tissues. In embodiments, the toxin SA antigen (e.g. Hla, Hlb, Hlg) may form a pore on a host cell, thereby lysing the host cell. For example, a toxin SA antigen may lyse a RBC, neutrophil, monocyte, or macrophage. In embodiments, the toxin SA antigen causes hemolysis or tissue damage at the infection site. In embodiments, the toxin SA antigen induces pro- inflammatory response in the host, thereby causing symptoms of SA infection (e.g. nausea, vomiting, abdominal pain, diarrhea). In embodiments, the toxin SA antigen damages the epidermal cells of the host, thereby causing blistering diseases (e.g. bullous impetigo and staphylococcal scalded skin syndrome (SSSS)). In embodiments, the toxin SA antigen includes a fragment or a portion of the toxin antigen. For example, the fragment or portion of the toxin antigen may induce generation of neutralizing antibodies targeting said toxin SA antigen.

[0154] In embodiments, the toxin SA antigen is α-hemolysin (Hla), toxic shock syndrome toxin (TSST), leukotoxin ED (LukED), protoxin subunit (LukS-PV), Leukotoxin AB, a phenol soluble modulin, or a combination thereof. In embodiments, the toxin SA antigen is α-hemolysin (Hla). In embodiments, the toxin SA antigen is TSST. In embodiments, the toxin SA antigen is LukED. In embodiments, the toxin SA antigen is LukS-PV. In embodiments, the toxin SA antigen is Leukotoxin AB. In embodiments, the toxin SA antigen is a phenol soluble modulin.

[0155] The term “Hla protein” or “Hla” as used herein includes any of the recombinant or naturally-occurring forms of α-hemolysin (Hla) protein, also known as alpha-HL, alpha-toxin, or variants or homologs thereof that maintain Hla activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to Hla). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identityacross the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring Hla protein. In embodiments, the Hla protein is substantially identical to the protein identified by the UniProt reference number P09616 or a variant or homolog having substantial identity thereto. In embodiments, the Hla protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 90% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 91% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 92% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 93% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 94% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 95% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 96% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 97% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 98% identity to SEQ ID NO:13. In embodiments, the Hla protein includes a sequence having at least 99% identity to SEQ ID NO:13. In embodiments, said Hla protein includes SEQ ID NO:13. In embodiments, said Hla protein is SEQ ID NO:13.

[0156] The term “TSST protein” or “TSST” as used herein includes any of the recombinant or naturally-occurring forms of toxic shock syndrome toxin (TSST) protein, also known as alpha- HL, alpha-toxin, or variants or homologs thereof that maintain TSST activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to TSST). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring TSST protein. In embodiments, the TSST protein is substantially identical to the protein identified by the UniProt reference number P06886 or a variant or homolog having substantial identity thereto. In embodiments, the TSST protein is substantially identical to the protein identified by the UniProt reference number A0A0K0VG33 or a variant or homolog having substantial identity thereto. In embodiments, the TSST protein is substantially identical to the protein identified by the UniProt reference number A0A0K0VFU2 or a variant or homolog having substantial identity thereto.

[0157] The term “LukED protein” or “LukED” as used herein includes any of the recombinant or naturally-occurring forms of leukotoxin ED (LukED) protein, also known as Bi-component leukocidin LukED subunit D (LukD), Bi-component leukocidin LukED subunit E (LukE), or variants or homologs thereof that maintain LukED activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to LukED). In embodiments, LukED protein refers to one or both subunits of LukED. Thus, in embodiments, LukED refers to LukE, LukD, or a combination thereof. In embodiments, LukED refers to LukE. In embodiments, LukED refers to LukD. In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring LukED protein. In embodiments, the LukED protein is substantially identical to the protein identified by the UniProt reference number A0A9Q4UW94 or a variant or homolog having substantial identity thereto. In embodiments, the LukED protein is substantially identical to the protein identified by the UniProt reference number A0A9Q2TTT2 or a variant or homolog having substantial identity thereto.

[0158] In embodiments, the LukE protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 90% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 91% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 92% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 93% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 94% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 95% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 96% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 97% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 98% identity to SEQ ID NO:14. In embodiments, the LukE protein includes a sequence having at least 99% identity to SEQ ID NO:14. In embodiments, said LukE protein includes SEQ ID NO:14. In embodiments, said LukE protein is SEQ ID NO:14.

[0159] In embodiments, the LukD protein includes a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:15. In embodiments, the LukD protein includes a sequence having at least 90% identity to SEQ ID NO:15. In embodiments, theLukD protein includes a sequence having at least 91% identity to SEQ ID NO:15. In embodiments, the LukD protein includes a sequence having at least 92% identity to SEQ ID NO:15. In embodiments, the LukD protein includes a sequence having at least 93% identity to SEQ ID NO:15. In embodiments, the LukD protein includes a sequence having at least 94% identity to SEQ ID NO:15. In embodiments, the LukD protein includes a sequence having at least 95% identity to SEQ ID NO:15. In embodiments, the LukD protein includes a sequence having at least 96% identity to SEQ ID NO:15. In embodiments, the LukD protein includes a sequence having at least 97% identity to SEQ ID NO:15. In embodiments, the LukD protein includes a sequence having at least 98% identity to SEQ ID NO:15. In embodiments, the LukD protein includes a sequence having at least 99% identity to SEQ ID NO:15. In embodiments, said LukD protein includes SEQ ID NO:15. In embodiments, said LukD protein is SEQ ID NO:15.

[0160] The term “LukS-PV protein” or “LukS-PV” as used herein includes any of the recombinant or naturally-occurring forms of protoxin subunit (LukS-PV) protein, or variants or homologs thereof that maintain LukS-PV activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to LukS-PV). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring LukS-PV protein. In embodiments, the LukS-PV protein is substantially identical to the protein identified by the UniProt reference number B1Q037 or a variant or homolog having substantial identity thereto. In embodiments, the LukS-PV protein is substantially identical to the protein identified by the UniProt reference number A0A1J0CYG0 or a variant or homolog having substantial identity thereto.

[0161] The term “LukAB protein” or “LukAB” as used herein includes any of the recombinant or naturally-occurring forms of leukotoxin AB (LukAB) protein, also known as LukGH, Bi- component leukocidin LukGH, Bi-component leukocidin LukGH subunit G, Bi-component leukocidin LukGH subunit H, LukGH, or variants or homologs thereof that maintain LukAB activity (e.g. within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to LukAB). In some aspects, the variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring LukAB protein. In embodiments, the LukAB protein is substantially identical to the protein identified by the UniProt reference number A0A6A9GWK6 or a variant or homologhaving substantial identity thereto. In embodiments, the LukAB protein is substantially identical to the protein identified by the UniProt reference number A0A6G4N894 or a variant or homolog having substantial identity thereto.

[0162] “Phenol soluble modulin” refers to a family of toxin proteins expressed by SA, including PSMα 1-4, PSMβ 1-2, PSMγ, PSMδ, PSMε, and PSM-mec. In embodiments, the PSMα 1 protein is substantially identical to the protein identified by the UniProt reference number P0C7Y0 or a variant or homolog having substantial identity thereto. In embodiments, the PSMα 2 protein is substantially identical to the protein identified by the UniProt reference number P0C7Z2 or a variant or homolog having substantial identity thereto. In embodiments, the PSMα 3 protein is substantially identical to the protein identified by the UniProt reference number P0C804 or a variant or homolog having substantial identity thereto. In embodiments, the PSMα 4 protein is substantially identical to the protein identified by the UniProt reference number P0C817 or a variant or homolog having substantial identity thereto. In embodiments, the PSM-mec protein is substantially identical to the protein identified by the UniProt reference number D5MS78 or a variant or homolog having substantial identity thereto.

[0163] In embodiments, wherein the vaccine provided herein includes a non-toxin SA antigen and a toxin SA antigen, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:2 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:3 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:4 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:5 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:6 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:7 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:8 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:9 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:10 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:11 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:12 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:13 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxinSA antigen is from about 1:14 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:15 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:16 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:17 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:19 to about 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:19 to about 1:20.

[0164] In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:19. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:18. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:17. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:16. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:15. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:14. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:13. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:12. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:11. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:10. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:9. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:8. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:7. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:6. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:5. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:4. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:3. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is from about 1:1 to about 1:2. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, or 1:20. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is 1:2. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is 1:5. In embodiments, the ratio of the toxin SA antigen to the non-toxin SA antigen is 1:10.

[0165] In embodiments, the vaccine does not include a toxin SA antigen.

[0166] In embodiments, the IL-17 activating adjuvant is CAF01, MPLA, a TLR7 agonist, betaglucan, Curdlan, synthetic cord factor (TDB), diphtheria toxoid, pertussis toxoid, Poly IC, flagellin from Salmonella typhimurium, flagellin from vibrio cholera, PAM2CSK4, PAM3CSK4, a CpG sequence, R484 (Resiquimod), cholera toxin, ionomycin, phorbol 12- myristate 13-acetate (PMA), or a combination thereof. In embodiments, the IL-17 activating adjuvant is CAF01. In embodiments, the IL-17 activating adjuvant is MPLA. In embodiments, the IL-17 activating adjuvant is a TLR7 agonist. In embodiments, the IL-17 activating adjuvant is betaglucan. In embodiments, the IL-17 activating adjuvant is Curdlan. In embodiments, the IL- 17 activating adjuvant is TDB. In embodiments, the IL-17 activating adjuvant is diphtheria toxoid. In embodiments, the IL-17 activating adjuvant is pertussis toxoid. In embodiments, the IL-17 activating adjuvant is Poly IC. In embodiments, the IL-17 activating adjuvant is Flagellin from Salmonella typhimurium. In embodiments, the IL-17 activating adjuvant is Flagellin from vibrio cholera. In embodiments, the IL-17 activating adjuvant is PAM2CSK4. In embodiments, the IL-17 activating adjuvant is PAM3CSK4. In embodiments, the IL-17 activating adjuvant is a CpG sequence. In embodiments, the IL-17 activating adjuvant is R484 (Resiquimod). In embodiments, the IL-17 activating adjuvant is Cholera toxin. In embodiments, the IL-17 activating adjuvant is ionomycin. In embodiments, the IL-17 activating adjuvant is PMA. In embodiments, the IL-17 activating adjuvant is ionomycin and PMA.

[0167] “CAF01 refers to an adjuvant composition including a combination of TBD and DDA. TBD, also known as trehalose-6,6-dibehenate, or the like, refers in the usual and customary sense, to [(2R,3S,4S,5R,6R)-6-[(2R,3R,4S,5S,6R)-6-(docosanoyloxymethyl)-3,4,5- trihydroxyoxan-2-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methyl docosanoate (CAS registry number 66758-35-8). DDA, or the like, refers in the usual and customary sense, to dimethyldioctadecyl- ammonium (CAS registry number 14357-21-2). In embodiments, DDA may refer to the salt form including dimethyldioctadecylazanium bromide or dimethyldioctadecylazanium chloride. In embodiments, CAF01 includes a weight ratio 5:1 DDA to TBD. TDB is commonly used as an immunomodulator and in embodiments can induce an immune response, thereby generating IgG1 and / or IgG2 antibodies. TDB is a synthetic analogue to the immune stimulatory component of the mycobacterial cell wall often referred to as “cord factor”. In embodiments, in an aqueous environment, DDA can self-assemble into closed vesicular bilayers (liposomes).

[0168] “MPLA”, also known as monophosphoryl lipid A, or the like, refers in the usual and customary sense, to ammonium (2R,3S,4R,5R,6R)-6-(((2R,3S,4R,5R,6S)-3,6-dihydroxy-5-((R)- 3-hydroxytetradecanamido)-4-(((R)-3-hydroxytetradecanoyl)oxy)tetrahydro-2H-pyran-2- yl)methoxy)-2-(hydroxymethyl)-5-((R)-3-(tetradecanoyloxy)tetradecanamido)-4-(((R)-3- (tetradecanoyloxy)tetradecanoyl)oxy)tetrahydro-2H-pyran-3-yl hydrogen phosphate (CAS registry number 1246298-63-4). MPLA may be derived from bacterial lipid A or chemically synthetized.

[0169] “TLR7 agonist” is used in accordance to its plain ordinary meaning in the art and refers to a molecule capable of inducing an immune response by activating toll-like receptor 7 (TLR7), typically through the MYD88-dependent pathway or caspase-dependent mitochondrial pathway. In embodiments, TLR7 agonists include gardiquimod, imiquimod, vesatolimod, LHC165, DSP- 0509, or AZD8848.

[0170] “Betaglucan”, also referred to as beta-glucan or β-glucan, refers to a β-D-glucose polysaccharide including D-glucose units linked by β-type glycosidic bonds. For example, a betaglucan may include D-glucose monomer units attached by β- 1,3, 1,4 or 1,6 glycosidic linkages. In embodiments, the betaglucan is curdlan. “Curdlan” is used in accordance to its plain ordinary meaning in the art and refers to a linear beta-1,3-glucan polymer formed of repeating glucose monomer units connected by β- 1,3 glycosidic linkages. Curdlan is a high molecular- weight polymer, having a molecular weight of up to about 2,000,000 Da.

[0171] “Diphtheria toxoid” is used in accordance to its plain ordinary meaning in the art and refers to a modified form of diphtheria toxin which is no longer toxic. In embodiments, diphtheria toxin is can be identified by its UniProt reference number P00587. In embodiments, the diphtheria toxin is chemically modified or modified by heat treatment. In embodiments, the administration of the diphtheria toxoid to a subject induces an immune response. In embodiments, the diphtheria toxoid is covalently attached to an antigen (e.g. a non-toxin SA antigen, a toxin SA antigen).

[0172] “Pertussis toxoid” is used in accordance to its plain ordinary meaning in the art and refers to a modified form of pertussis toxin which is no longer toxic. Pertussis toxin refers to an exotoxin complex including 6 protein subunits including an A subunit and five B subunits. In embodiments, the pertussis toxoid is generated by treating pertussis toxin with hydrogen peroxide, formalin, or glutaraldehyde.

[0173] “Poly IC”, also known as polyinosinic:polycytidylic acid or poly I:C, refers to a synthetic, double-stranded RNA that mimics viral RNA and induces an immune response. The double-stranded DNA includes mismatched bases, including a first strand composed of a polymer of inosinic acid, and the second strand composed of a polymer of cytidylic acid. In embodiments, PolyIC induces an immune response by binding to toll-like receptor 3 (TLR3) expressed on B-cells, macrophages, or dendritic cells.

[0174] “Flagellin from Salmonella typhimurium” refers to a protein subunit when complexed to other subunits form filaments of Salmonella typhimurium flagella. Typically, flagellin subunits arrange in a hollow cylindrical structure for filament formation. In embodiments, flagellin from Salmonella typhimurium can be identified by its UniProt reference number P06179.

[0175] “Flagellin from vibrio cholera” refers to one or a combination of the five flagellin subunits FlaA, FlaB, FlaC, FlaD, and FlaE that when complexed, form a vibrio cholera bacterial flagella. In embodiments, FlaA is identified by its UniProt reference number P0C6C3. In embodiments, FlaB is identified by its UniProt reference number P0C6C4. In embodiments, FlaC is identified by its UniProt reference number P0C6C5. In embodiments, FlaD is identified by its UniProt reference number P0C6C6. In embodiments, FlaE is identified by its UniProt reference number P0C6C7.

[0176] “PAM2CSK4”, also known as Pam2CysSerLys4, or the like, refers in the usual and customary sense, to (2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2- [[(2S)-2-[[(2R)-2-amino-3-[2,3-di(hexadecanoyloxy)propylsulfanyl]propanoyl]amino]-3- hydroxypropanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoic acid (CAS registry number 868247-72-7). PAM2CSK4 is a synthetic diacylated lipopeptide that functions as an activator of the transcription factor NF-κB. In embodiments, PAM2CSK4 is capable of mimicking the acylated amino terminus of bacterial lipopeptides and binds the TLR2 / TLR6 heterodimer on the surface of cells.

[0177] “Pam3CSK4”, also known as Pam3CysSerLys4, or the like, refers in the usual and customary sense, to (2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2- [[(2S)-2-[[(2R)-3-[2,3-di(hexadecanoyloxy)propylsulfanyl]-2- (hexadecanoylamino)propanoyl]amino]-3- hydroxypropanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoic acid;2,2,2-trifluoroacetic acid (CAS registry number 112208-01-2). Pam3CSK4 is a synthetictriacylated lipopeptide that functions as a ligand of TLR2 / TLR1. In embodiments, Pam3CSK4 functions as an activator of the transcription factor NF-κB. In embodiments, Pam3CSK4 is capable of mimicking the acylated amino terminus of bacterial lipopeptides.

[0178] “CpG sequence” refers to a single-stranded oligodeoxynucleotide (ODN) including a 5’ C nucleotide connected to a 3’ G nucleotide through a phosphodiester internucleotide linkage or a phosphodiester derivative internucleotide linkage. In embodiments, the term “CpG sequence” refers to a nucleic acid in which a 5’ G nucleotide connected to a 3’ C nucleotide through a phosphodiester internucleotide linkage or a phosphodiester derivative internucleotide linkage (aka, a “GpC nucleic acid sequence”). In embodiments, a CpG includes a phosphodiester internucleotide linkage. In embodiments, a CpG includes a phosphodiester derivative internucleotide linkage. In embodiments, a CpG includes a phosphorothioate linkage.

[0179] As used herein, the term "Class A CpG ODN” or “A-class CpG ODN” or “D-type CpG ODN” or “Class A CpG DNA sequence” is used in accordance with its common meaning in the biological and chemical sciences and refers to a CpG motif including oligodeoxynucleotide including one or more of poly-G sequence at the 5’, 3’, or both ends; an internal palindrome sequence including CpG motif; or one or more phosphodiester derivatives linking deoxynucleotides. In embodiments, a Class A CpG ODN includes poly-G sequence at the 5’, 3’, or both ends; an internal palindrome sequence including CpG motif; and one or more phosphodiester derivatives linking deoxynucleotides. In embodiments, the phosphodiester derivative is phosphorothioate. Examples of Class A CpG ODNs include ODN D19, ODN 1585, ODN 2216, and ODN 2336.

[0180] As used herein, the term "Class B CpG ODN” or “B-class CpG ODN” or “K-type CpG ODN” or “Class B CpG DNA sequence” is used in accordance with its common meaning in the biological and chemical sciences and refers to a CpG motif including oligodeoxynucleotide including one or more of a 6mer motif including a CpG motif; phosphodiester derivatives linking all deoxynucleotides. In embodiments, a 6mer motif comprises 5’-PuPyCGPyPu-3’ (SEQ ID NO: 15), where Pu represents a purine containing nucleobase (e.g., A or G) and Py represents a pyrimidine containing nucleobase (e.g., T / U or C). In embodiments, a Class B CpG ODN includes one or more copies of a 6mer motif including a CpG motif and phosphodiester derivatives linking all deoxynucleotides. In embodiments, the phosphodiester derivative is phosphorothioate. In embodiments, a Class B CpG ODN includes one 6mer motif including a CpG motif. In embodiments, a Class B CpG ODN includes two copies of a 6mer motifincluding a CpG motif. In embodiments, a Class B CpG ODN includes three copies of a 6mer motif including a CpG motif. In embodiments, a Class B CpG ODN includes four copies of a 6mer motif including a CpG motif. Examples of Class B CpG ODNs include ODN 1668, ODN 1826, ODN 2006, and ODN 2007.

[0181] As used herein, the term "Class C CpG ODN” or “C-class CpG ODN” ” or “C-type CpG DNA sequence” is used in accordance with its common meaning in the biological and chemical sciences and refers to an oligodeoxynucleotide including a palindrome sequence including a CpG motif and phosphodiester derivatives (phosphorothioate) linking all deoxynucleotides. Examples of Class C CpG ODNs include ODN 2395 and ODN M362.

[0182] “R848”, also known as Resiquimod or the like, refers in the usual and customary sense, to 1-[4-amino-2-(ethoxymethyl)imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol (CAS registry number 144875-48-9). In embodiments, R848 functions by as an agonist for toll-like receptor 7 and 8.

[0183] “Cholera toxin” as used herein refers to a non-toxic subunit of cholera toxin. In embodiments, cholera toxin refers to nontoxic subunit B of cholera toxin. In embodiments, subunit B of cholera is identified by its UniProt reference number P01556.

[0184] “Ionomycin” or the like, refers in the usual and customary sense, to (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-19,21-Dihydroxy-22-{(2S,2′R,5S,5′S)-5′-[(1R)- 1-hydroxyethyl]-2,5′-dimethyloctahydro-2,2′-bifuran-5-yl}-4,6,8,12,14,18,20-heptamethyl-11- oxido-9-oxodocosa-10,16-dienoic acid (CAS registry number 56092-81-0). Ionomycin is an ionophore capable of binding divalent cations including calcium ions, magnesium ions and cadmium ions. In embodiments, ionomycin refers to the free acid compound or as the Ca2+salt.

[0185] “Phorbol 12-myristate 13-acetate” also known as PMA or the like, refers in the usual and customary sense, to (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b-Dihydroxy-3- (hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-9aH- cyclopropa[3,4]benzo[1,2-e]azulene-9,9a-diyl 9a-acetate 9-tetradecanoate (CAS registry number 16561-29-8). In embodiments, PMA has inflammatory functions and activates protein kinase C (PKC).

[0186] In embodiments, the non-toxin SA antigen is IsdB and the IL-17 activating adjuvant is CAF01. In embodiments, the non-toxin SA antigen is IsdB, the IL-17 activating adjuvant is MPLA. In embodiments, the non-toxin SA antigen is IsdB and the IL-17 activating adjuvant isTDB. In embodiments, the non-toxin SA antigen is IsdB and the IL-17 activating adjuvant is pertussis toxoid. In embodiments, the non-toxin SA antigen is IsdB and sdrE and the IL-17 activating adjuvant is CAF01. In embodiments, the the non-toxin SA antigen is IsdB and the IL- 17 activating adjuvant is ionomycin and PMA. In embodiments, the non-toxin SA antigen is MntC and the IL-17 activating adjuvant is CAF01. In embodiments, the non-toxin SA antigen is IsdA and the IL-17 activating adjuvant is CAF01. In embodiments, the non-toxin SA antigen is FhuD2 and the IL-17 activating adjuvant is CAF01.

[0187] In embodiments, the vaccine further comprises alum. The term “alum” is used in accordance to its plain ordinary meaning in the and refers to a hydrated double sulfate salt of aluminum with the general formula XAl2·12 H2O, wherein X is a monovalent cation. In embodiments, X is potassium or ammonium. In embodiments, alum refers to potassium alum, wherein potassium alum has the formula KAl2·12 H2O.

[0188] For the vaccine provided herein, in embodiments, a dosage unit of the vaccine includes from about 200 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 225 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 250 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 275 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 300 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 325 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 350 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 375 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 400 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 425 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 450 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 475 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 500 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 525 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 550 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 575 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 600 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccineincludes from about 625 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 650 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 675 to about 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 675 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 650 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 625 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 600 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 575 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 550 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 525 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 500 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 475 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 450 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 425 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 400 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 375 to about micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 350 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 325 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 300 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 275 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 250 micrograms of alum. In embodiments, a dosage unit of the vaccine includes from about 200 to about 225 micrograms of alum. In embodiments, a dosage unit of the vaccine includes about 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700 micrograms of alum. In embodiments, a dosage unit of the vaccine includes about 500 micrograms of alum. In embodiments, a dosage unit of the vaccine includes 500 micrograms of alum.

[0189] For the vaccine provided herein, in embodiments, a dosage unit of the vaccine includes from about 1 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 20 to about 400 micrograms of IL-17 activating adjuvant.In embodiments, a dosage unit of the vaccine includes from about 40 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 60 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 80 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 100 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 120 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 140 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 160 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 180 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 200 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 220 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 240 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 260 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 280 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 300 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 320 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 340 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 360 to about 400 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 380 to about 400 micrograms of IL-17 activating adjuvant.

[0190] In embodiments, a dosage unit of the vaccine includes from about 1 to about 380 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 360 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 340 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 320 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 300 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 280 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 260 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 240 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 220 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 200 micrograms of IL- 17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 180 micrograms of IL-17 activating adjuvant.

[0191] In embodiments, a dosage unit of the vaccine includes from about 1 to about 160 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 140 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 120 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 100 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 80 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 60 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 40 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 1 to about 20 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes about 1, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, or 400 micrograms of IL-17 activating adjuvant.

[0192] For the vaccine provided herein, in embodiments, a dosage unit of the vaccine includes from about 50 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 60 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 70 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 80 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 90 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 100 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 110 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 120 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 130 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 140to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 150 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 160 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 170 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 180 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 190 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 200 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 210 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 220 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 230 to about 250 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 240 to about 250 micrograms of IL-17 activating adjuvant.

[0193] In embodiments, a dosage unit of the vaccine includes from about 50 to about 240 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to 230 about micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 220 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 210 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 200 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 190 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 180 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 170 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 160 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 150 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 140 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 130 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 120 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 110 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of thevaccine includes from about 50 to about 100 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 90 micrograms of IL- 17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 80 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 70 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes from about 50 to about 60 micrograms of IL-17 activating adjuvant. In embodiments, a dosage unit of the vaccine includes about 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 micrograms of IL- 17 activating adjuvant.

[0194] For the vaccine provided herein, in embodiments, a dosage of the vaccine includes from about 1 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 10 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 20 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 30 to about 200 micrograms non- toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 40 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 50 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 60 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 70 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 80 to about 200 micrograms non- toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 90 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 100 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 110 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 120 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 130 to about 200 micrograms non- toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 140 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 150 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 160 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 170 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 180 to about 200 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 190 to about 200 micrograms non-toxin SA antigen.

[0195] In embodiments, a dosage of the vaccine includes from about 1 to about 190 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 180 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 170 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 160 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 150 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 140 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 130 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 120 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 110 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 100 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 90 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 80 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 70 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 60 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 50 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 40 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 30 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 20 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 1 to about 10 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes about 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 micrograms non-toxin SA antigen.

[0196] In embodiments, a dosage of the vaccine includes from about 30 to about 50 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 32 to about 50 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 34 to about 50 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 36 to about 50 micrograms non-toxin SA antigen. Inembodiments, a dosage of the vaccine includes from about 38 to about 50 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 40 to about 50 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 42 to about 50 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 44 to about 50 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 46 to about 50 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 48 to about 50 micrograms non-toxin SA antigen.

[0197] In embodiments, a dosage of the vaccine includes from about 30 to about 48 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 30 to about 46 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 30 to about 44 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 30 to about 42 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 30 to about 40 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 30 to about 38 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 30 to about 36 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 30 to about 34 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes from about 30 to about 32 micrograms non-toxin SA antigen. In embodiments, a dosage of the vaccine includes about 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or 50 micrograms non-toxin SA antigen.

[0198] In embodiments, the pH of the vaccine is from about 6.0 to about 8.0. In embodiments, the pH of the vaccine is from about 6.2 to about 8.0. In embodiments, the pH of the vaccine is from about to about 8.0. In embodiments, the pH of the vaccine is from about 6.4 to about 8.0. In embodiments, the pH of the vaccine is from about 6.6 to about 8.0. In embodiments, the pH of the vaccine is from about 6.8 to about 8.0. In embodiments, the pH of the vaccine is from about 7.0 to about 8.0. In embodiments, the pH of the vaccine is from about 7.2 to about 8.0. In embodiments, the pH of the vaccine is from about 7.4 to about 8.0. In embodiments, the pH of the vaccine is from about 7.6 to about 8.0. In embodiments, the pH of the vaccine is from about 7.8 to about 8.0.

[0199] In embodiments, the pH of the vaccine is from about 6.0 to about 7.8. In embodiments, the pH of the vaccine is from about 6.0 to about 7.6. In embodiments, the pH of the vaccine isfrom about 6.0 to about 7.8. In embodiments, the pH of the vaccine is from about 6.0 to about 7.4. In embodiments, the pH of the vaccine is from about 6.0 to about 7.2. In embodiments, the pH of the vaccine is from about 6.0 to about 7.8. In embodiments, the pH of the vaccine is from about 6.0 to about 7.0. In embodiments, the pH of the vaccine is from about 6.0 to about 7.8. In embodiments, the pH of the vaccine is from about 6.0 to about 6.8. In embodiments, the pH of the vaccine is from about 6.0 to about 6.6. In embodiments, the pH of the vaccine is from about 6.0 to about 6.4. In embodiments, the pH of the vaccine is from about 6.0 to about 6.2. In embodiments, the pH of the vaccine is from about 6.0, 6.2, 6.4, 6.6, 6.8, 7.0, 7.2, 7.4, 7.6, 7.8, or 8.0. In embodiments, the pH of the vaccine is about 7.0. In embodiments, the pH of the vaccine is 7.0.

[0200] In aspects, the vaccine further comprises a surfactant (e.g., hexadecylamine, octadecylamine, lysolecithin, dimethyldioctadecylammonium bromide, N,N-dioctadecyl-N’,N- bis(2-hydroxy-ethylpropane diamine), methoxyhexadecyl glycerol, pluronic polyols), polyanions (e.g., pyran, dextran sulfate, poly IC, polyacrylic acid, Carbopol), peptides (e.g., muramyl dipeptide, aimethylglycine), tuftsin, oil emulsions, B peptide subunits of E. coli, or a combination of two or more thereof. In aspects, the adjuvant comprises a surfactant.

[0201] The vaccines and compositions may be lyophilized or in aqueous form, i.e., solutions or suspensions. Liquid formulations allow the compositions to be administered direct from their packaged form, without the need for reconstitution in an aqueous medium, and are thus ideal for injection. Suitable aqueous media for an aqueous form of the vaccine or for reconstituting a lyophilized vaccine include phosphate buffered saline (PBS), sterile water, distilled water, 0.4% sodium chloride, and 0.0% sodium chloride. In embodiments, the media for an aqueous form of the vaccine or for reconstituting a lyophilized is PBS. In embodiments, the media for an aqueous form of the vaccine or for reconstituting a lyophilized is sterile water. In embodiments, the media for an aqueous form of the vaccine or for reconstituting a lyophilized is distilled water.

[0202] Compositions may be presented in vials, or they may be presented in ready filled syringes or needle-free injectors. The syringes may be supplied with or without needles. A syringe will include a single dose of the composition, whereas a vial may include a single dose or multiple doses (e.g., 2, 3, or 4 doses). In aspects, the dose is for a human and may be administered by injection. Vaccines may be packaged in unit dose form or in multiple dose form (e.g.2, 3, or 4 doses). For multiple dose forms, vials can be pre-filled syringes. Effective dosagevolumes can be routinely established, but a typical human dose of the composition has an injection volume of 0.1 mL to 1 mL.

[0203] In an aspect is provided a vaccine including a Staphylococcus aureus (SA) antigen and an IL-17 activating adjuvant. In embodiments, the SA antigen is expressed on the surface of an SA bacteria. In embodiments, the SA antigen is IsdB, mntC, IsdA, or a combination thereof. In embodiments, the SA antigen is IsdB. In embodiments, the SA antigen is mntC. In embodiments, the SA antigen is IsdA.

[0204] In embodiments, the SA antigen is attached to the IL-17 activating adjuvant. In embodiments, the SA antigen is non-covalently attached to the IL-17 activating adjuvant. In embodiments, the SA antigen is covalently attached to the IL-17 activating adjuvant. In embodiments, the SA antigen is covalently attached to the IL-17 activating adjuvant by a peptide linker. In embodiments, the peptide linker is about 3 amino acid residues to about 50 amino acid residues in length.

[0205] For the vaccine provided herein, in embodiments, the IL-17 activating adjuvant includes CAF01, MPLA, a TLR7 agonist, betaglucan, Curdlan, synthetic cord factor (TDB), diphtheria toxoid, pertussis toxoid, Poly IC, Flagellin from Salmonella typhimurium, Flagellin from vibrio cholera, PAM2CSK4, PAM3CSK4, a Bacterial CpG sequence, R484 (Resiquimod), Cholera toxin, or a combination thereof. In embodiments, the IL-17 activating adjuvant includes CAF01. In embodiments, the IL-17 activating adjuvant includes MPLA. In embodiments, the IL- 17 activating adjuvant includes a TLR7 agonist. In embodiments, the IL-17 activating adjuvant includes betaglucan. In embodiments, the IL-17 activating adjuvant includes Curdlan. In embodiments, the IL-17 activating adjuvant includes synthetic cord factor (TDB). In embodiments, the IL-17 activating adjuvant includes diphtheria toxoid. In embodiments, the IL- 17 activating adjuvant includes pertussis toxoid. In embodiments, the IL-17 activating adjuvant includes Poly IC. In embodiments, the IL-17 activating adjuvant includes Flagellin from Salmonella typhimurium. In embodiments, the IL-17 activating adjuvant includes Flagellin from vibrio cholera. In embodiments, the IL-17 activating adjuvant includes PAM2CSK4, PAM3CSK4, a CpG sequence, R484 (Resiquimod), Cholera toxin. In embodiments, the IL-17 activating adjuvant includes PAM2CSK4. In embodiments, the IL-17 activating adjuvant includes PAM3CSK4. In embodiments, the IL-17 activating adjuvant includes a CpG sequence. In embodiments, the IL-17 activating adjuvant includes R484 (Resiquimod). In embodiments, the IL-17 activating adjuvant includes Cholera toxin.

[0206] In embodiments, the vaccine further includes alum.

[0207] In embodiments, the IL-17 activating adjuvant includes Poly IC and the vaccine further includes alum. In embodiments, the IL-17 activating adjuvant includes Flagellin from Salmonella typhimurium and Flagellin from vibrio cholera. In embodiments, the IL-17 activating adjuvant includes Flagellin from Salmonella typhimurium or Flagellin from vibrio cholera.

[0208] In embodiments, the IL-17 activating adjuvant includes PAM2CSK4 and the vaccine further includes Alum. In embodiments, the IL-17 activating adjuvant includes PAM3CSK4 and the vaccine further includes Alum. In embodiments, the IL-17 activating adjuvant includes CpG sequences and the vaccine further includes Alum. In embodiments, the IL-17 activating adjuvant includes R484 and the vaccine further includes Alum. In embodiments, the IL-17 activating adjuvant includes Choloera toxin and the vaccine further includes Alum.

[0209] In embodiments, the IL-17 activating adjuvant includes pertussis toxoid. In embodiments, the IL-17 activating adjuvant includes CAF01. In embodiments, the IL-17 activating adjuvant includes MPLA. In embodiments, the IL-17 activating adjuvant includes TDB.

[0210] For the vaccine provided herein, in embodiments, the SA antigen is IsdB and the IL-17 activating adjuvant is CAF01.

[0211] For the vaccine provided herein, in embodiments, the SA antigen is IsdB, the IL-17 activating adjuvant is MPLA, and the vaccine further includes alum.

[0212] For the vaccine provided herein, in embodiments, the SA antigen is IsdB, the IL-17 activating adjuvant is TDB, and the vaccine further includes alum.

[0213] For the vaccine provided herein, in embodiments, the SA antigen is IsdB, the IL-17 activating adjuvant is pertussis toxoid, and the SA antigen is attached to the IL-17 activating adjuvant. PHARMACEUTICAL COMPOSITIONS

[0214] In an aspect is provided a pharmaceutical composition including a therapeutically or prophylactically effective amount of the vaccine provided herein including embodiments thereof and a pharmaceutically acceptable excipient. In embodiments, the pharmaceutical composition includes a therapeutically effective amount of the vaccine provided herein including embodiments thereof and a pharmaceutically acceptable excipient. In embodiments, thepharmaceutical composition includes a prophylactically effective amount of the vaccine provided herein including embodiments thereof and a pharmaceutically acceptable excipient.

[0215] In embodiments, the compositions provided herein are used for a therapeutic purpose. In some embodiments, a therapeutic purpose encompasses a prophylactic purpose (a purpose of preventing infection by SA, or occurrence of a disease or condition associated with infection by SA) and a treatment purpose (a purpose of treating infection by SA, or an existing disease or condition associated with infection by SA).

[0216] In some embodiments, a composition can be a vaccine or a composition thereof, i.e. a composition that contains the vaccine provided herein including embodiments thereof and optionally a pharmaceutically acceptable carrier. The vaccine or vaccine composition can be used to prevent and / or treat a disease or condition associated with infection by SA or an infection by. In some embodiments, the vaccine or vaccine composition includes a non-toxin SA antigen and an IL-17 activating adjuvant. In some embodiments, the vaccine, when administered to a subject, can induce an immune response, i.e. immunogenic.

[0217] In one aspect, the vaccine disclosed herein can be formulated in a pharmaceutical composition. In one embodiment, the pharmaceutical composition can further contain a pharmaceutically acceptable excipient and / or a pharmaceutically acceptable carrier.

[0218] In some embodiments, pharmaceutical compositions can have a non-toxin SA antigen, an IL-17 activating adjuvant and further contain pharmaceutically acceptable excipients or additives depending on the route of administration. Examples of such excipients or additives include water, a pharmaceutical acceptable organic solvent, collagen, polyvinyl alcohol, polyvinylpyrrolidone, a carboxyvinyl polymer, carboxymethylcellulose sodium, polyacrylic sodium, sodium alginate, water-soluble dextran, carboxymethyl starch sodium, pectin, methyl cellulose, ethyl cellulose, xanthan gum, gum Arabic, casein, gelatin, agar, diglycerin, glycerin, propylene glycol, polyethylene glycol, Vaseline, paraffin, stearyl alcohol, stearic acid, human serum albumin (HSA), mannitol, sorbitol, lactose, a pharmaceutically acceptable surfactant and the like. Additives used can be chosen from, but not limited to, the above or combinations thereof, as appropriate, depending on the dosage form of the present disclosure.

[0219] Formulation of the pharmaceutical compositions of the present disclosure can vary according to the route of administration selected (e.g., solution, emulsion). Routes ofadministration can be, for example, intraperitoneal, intramuscular, subcutaneous, intradermal, intranasal, or oral.

[0220] In some embodiments, the composition can include a cryoprotectant agent. Non- limiting examples of cryoprotectant agents include a glycol (e.g., ethylene glycol, propylene glycol, and glycerol), dimethyl sulfoxide (DMSO), formamide, sucrose, trehalose, dextrose, and any combinations thereof.

[0221] In some embodiments, the formulation is a controlled release formulation. The term “controlled release formulation” includes sustained release and time-release formulations. Controlled release formulations are well-known in the art. These include excipients that allow for sustained, periodic, pulse, or delayed release of the composition. Controlled release formulations include, without limitation, embedding of the composition into a matrix; enteric coatings; micro- encapsulation; gels and hydrogels; implants; and any other formulation that allows for controlled release of a composition.

[0222] In one aspect is provided a kit of parts having a vaccine composition provided herein including embodiments thereof. The kit can further contain a document or an instruction that describes a protocol administering the vaccine composition to a subject in need thereof.

[0223] Therapeutic formulations described herein can be prepared for storage by mixing the non-toxin SA antigen and IL-18 activating adjuvant having the desired degree of purity with optional physiologically acceptable carriers, excipients or stabilizers. Acceptable carriers, excipients, or stabilizers can be nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or non-ionic surfactants such as TWEEN™, PLURONICS™ or polyethylene glycol (PEG).

[0224] The formulation herein may also contain more than one active compound (e.g., a second, third, fourth, etc. non-toxin SA antigen, a toxin SA antigen), which may be selected for complementary activities that do not adversely affect each other. Such molecules can be suitably present in combination in amounts that can be effective for the purpose intended. METHODS

[0225] In an aspect is provided a method of treating or preventing an SA-associated disease in a subject in need of such treatment or prevention, the method including administering a therapeutically or prophylactically effective amount of the vaccine provided herein including embodiments thereof or the pharmaceutical composition provided herein including embodiments thereof to the subject. In embodiments, the method includes administering a therapeutically or prophylactically effective amount of the vaccine provided herein including embodiments thereof. In embodiments, the method includes administering a therapeutically or prophylactically effective amount of the pharmaceutical composition provided herein including embodiments thereof.

[0226] The term “SA-associated disease” refers to a disease or condition associated with infection by staphylococcus aureus. For example, in embodiments, an SA-associated disease is caused by infection by SA. In embodiments, an SA-associated disease is a result of infection by SA. In embodiments, the SA-associated disease is pneumonia, toxic shock syndrome, bloodstream infection, infective endocarditis, food poisoning, meningitis, an abscess, osteomyelitis, myositis, septic arthritis, a skin or soft tissue infection, or a combination thereof. In embodiments, the SA-associated disease is pneumonia. In embodiments, the SA-associated disease is toxic shock syndrome. In embodiments, the SA-associated disease is bloodstream infection. In embodiments, the SA-associated disease is infective endocarditis. In embodiments, the SA-associated disease is food poisoning. In embodiments, the SA-associated disease is meningitis. In embodiments, the SA-associated disease is an abscess. In embodiments, the SA- associated disease is osteomyelitis. In embodiments, the SA-associated disease is myositis. In embodiments, the SA-associated disease is septic arthritis. In embodiments, the SA-associated disease is a skin or soft tissue infection. Thus, in embodiments, pneumonia, toxic shock syndrome, bloodstream infection, infective endocarditis, food poisoning, meningitis, an abscess, osteomyelitis, myositis, septic arthritis, or a skin or soft tissue infection is associated with infection by staphylococcus is caused by or is a result of infection by SA. A person having ordinary skill in the art would therefore understand that pneumonia, toxic shock syndrome,bloodstream infection, infective endocarditis, food poisoning, meningitis, an abscess, osteomyelitis, myositis, septic arthritis, or a skin or soft tissue infection is associated with infection by staphylococcus.

[0227] In embodiments, the subject having an SA-associated disease is a subject that was previously exposed to SA prior to contracting the SA-associated disease. In embodiments, the subject having an SA-associated disease is a subject that was previously infected with SA prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA. In embodiments, the subject was previously infected by SA. In embodiments, the subject had overcome the previous infection. In embodiments, the previous infection caused the subject to contract a previous SA-associated disease. In embodiments, the subject had overcome the previous SA-associated disease. In embodiments, the previous SA-associated disease is pneumonia, toxic shock syndrome, bloodstream infection, infective endocarditis, food poisoning, meningitis, an abscess, osteomyelitis, myositis, septic arthritis, a skin or soft tissue infection, or a combination thereof. In embodiments, the subject was previously exposed to SA or previously infected by SA so that antibodies targeting an SA antigen were previously generated. Therefore, in embodiments, the subject may have a recall immune response when subsequently exposed to or infected by SA. In embodiments, the subject may have a recall immune response from the previous exposure to SA or previous infection by SA wherein non-neutralizing antibodies to a non-toxin SA antigen or a toxin SA antigen are produced. For example, in embodiments, the subject may have a recall immune response wherein non-neutralizing antibodies to any one of the non-toxin SA antigens or toxin SA antigens provided herein including embodiments thereof. In embodiments, the recall immune response inhibits IL-17 activity or INF-γ activity. In embodiments, the recall immune response inhibits cell T (e.g. CD4+T cell) and B cell activity. For example, in embodiments, the recall immune response may inhibit proliferation or differentiation of T cells and B cells, and / or inhibit generation of neutralizing antibodies targeting a non-toxin SA antigen or toxin SA antigen.

[0228] In embodiments, the subject was previously exposed to SA at least 1 month prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 2 months prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 4 months prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 6 months prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 8months prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 10 months prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 1 year prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 2 years prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 5 years prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 10 years prior to contracting the SA-associated disease. In embodiments, the subject was previously exposed to SA at least 20 years prior to contracting the SA-associated disease.

[0229] In embodiments, the previous infection occurred at least 1 month prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 2 months prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 4 months prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 6 months prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 8 months prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 10 months prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 1 year prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 2 years prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 5 years prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 10 years prior to the subject contracting the SA-associated disease. In embodiments, the previous infection occurred at least 20 years prior to the subject contracting the SA-associated disease.

[0230] In embodiments, the previous SA infection is a systemic infection. For example, in a systemic infection, the infection has spread to multiple organs or tissues. In embodiments, the previous SA infection is a skin infection. For example, the skin infection may cause a disease or condition including cellulitis or an abscess.

[0231] In embodiments, the vaccine is administered intraperitoneally, intramuscularly, subcutaneously, intradermally, intranasally, or orally. In embodiments, the vaccine is administered intraperitoneally. In embodiments, the vaccine is administered intramuscularly. In embodiments, the vaccine is administered subcutaneously. In embodiments, the vaccine isadministered intradermally. In embodiments, the vaccine is administered intranasally. In embodiments, the vaccine is administered orally.

[0232] In an aspect is provided a method of immunizing a subject susceptible to SA infection, including administering to the subject the vaccine provided herein including embodiments thereof or the pharmaceutical composition provided herein including embodiments thereof. In embodiments, the method includes administering to the subject the vaccine provided herein including embodiments thereof. In embodiments, the method includes administering to the subject the pharmaceutical composition provided herein including embodiments thereof.

[0233] In embodiments, the vaccine is administered under conditions such that antibodies directed to said non-toxin SA antigen or a functional fragment thereof are produced. In embodiments, the antibodies are neutralizing antibodies. For example, a neutralizing antibody binds an epitope of a non-toxin SA antigen, thereby decreasing or inhibiting the function of the non-toxin SA antigen. In embodiments, the antibodies are IgG1 antibodies. In embodiments, production of an antibody targeting a non-toxin SA antigen induces opsonization of the SA. In embodiments, production of an antibody targeting a non-toxin SA antigen induces phagocytosis of the SA.

[0234] According to the methods provided herein, the subject can be administered an effective amount of one or more of agents or compositions (e.g. vaccine) all of which are interchangeably used herein (e.g. vaccine, vaccine composition) provided herein. The terms “effective amount” and “effective dosage” are used interchangeably. The term “effective amount” is defined as any amount necessary to produce a desired effect (e.g., administering the vaccine to a subject and exhibiting an intended outcome of the vaccine). Effective amounts and schedules for administering the agent can be determined empirically by one skilled in the art. The dosage ranges for administration are those large enough to produce the desired effects, e.g. induction of immune response and more. The dosage should not be so large as to cause substantial adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like. Generally, the dosage can vary with the age, condition, sex, type of disease, the extent of the disease or disorder, route of administration, or whether other drugs are included in the regimen, and can be determined by one of skill in the art. The dosage can be adjusted by the individual physician in the event of any contraindications. Dosages can vary and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. For example, for the givenparameter, an effective amount can show an increase or decrease of at least 5%, 10%, 15%, 20%, 25%, 40%, 50%, 60%, 75%, 80%, 90%, or at least 100%. Efficacy can also be expressed as “- fold” increase or decrease. For example, a therapeutically effective amount can have at least a 1.2-fold, 1.5-fold, 2-fold, 5-fold, or more effect over a control. The exact dose and formulation can depend on the purpose of the treatment, and can be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols.1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Remington: The Science and Practice of Pharmacy, 20th Edition, Gennaro, Editor (2003), and Pickar, Dosage Calculations (1999)).

[0235] “Administration,” “administering” and the like, when used in connection with a composition refer both to direct administration, which may be administration to cells in vitro, administration to cells in vivo, administration to a subject by a medical professional or by self- administration by the subject and / or to indirect administration, which may be the act of prescribing a composition of the disclosure. In embodiments, the administration is in vivo. In embodiments, the administration is in vitro. When used herein in reference to a cell, administering refers to introducing a composition to the cell. Typically, an effective amount is administered, which amount can be determined by one of skill in the art. Any method of administration may be used. Compounds (e.g., the non-toxin SA antigen, IL-17 activating adjuvant, toxin SA antigen) may be administered to the cells by, for example, addition of the compounds to the cell culture media or injection in vivo. Administration to a subject can be achieved by, for example, intravascular injection, direct intratumoral delivery, and the like.

[0236] For the method provided herein, in embodiments, the subject was previously exposed to SA. In embodiments, the subject was previously infected by SA. In embodiments, the previous SA infection is a systemic infection. In embodiments, the previous SA infection is a skin infection.

[0237] In embodiments, the vaccine is administered intraperitoneally, intramuscularly, subcutaneously, intradermally, intranasally, or orally. In embodiments, the vaccine is administered intraperitoneally. In embodiments, the vaccine is administered intramuscularly. In embodiments, the vaccine is administered subcutaneously. In embodiments, the vaccine is administered intradermally. In embodiments, the vaccine is administered intranasally. In embodiments, the vaccine is administered orally.

[0238] In one aspect, the disclosures herewith provide a method of inducing an immune response against Staphylococcus aureus in a subject in need thereof. The method includes administering the vaccine provided herein including embodiments thereof to the subject.

[0239] In another aspect is provided a method of immunizing a subject from Staphylococcus aureus infection, including administering the vaccine provided herein including embodiments thereof to the subject.

[0240] In aspects are provided methods for delivering the vaccine provided herein including embodiments thereof to cells or a subject so as to provide a desired activity to the subject. In some embodiments, the vaccine includes an SA antigen and a IL-17 activating adjuvant. In some embodiments, the vaccine can be administered to a subject in an effective amount that is sufficient to achieve at least part of the intended effects in the subject. P EMBODIMENTS

[0241] P embodiment 1. A vaccine comprising a Staphylococcus aureus (SA) antigen and an IL-17 activating adjuvant.

[0242] P embodiment 2. The vaccine of P embodiment 1, wherein the SA antigen is expressed on the surface of an SA bacteria.

[0243] P embodiment 3. The vaccine of P embodiment 1 or 3, wherein the SA antigen is IsdB, mntC, IsdA, or a combination thereof.

[0244] P embodiment 4. The vaccine of any one of P embodiments 1 to 3, wherein the SA antigen is IsdB.

[0245] P embodiment 5. The vaccine of any one of P embodiments 1 to 4, wherein the SA antigen is attached to the IL-17 activating adjuvant.

[0246] P embodiment 6. The vaccine of P embodiment 5, wherein the SA antigen is covalently attached to the IL-17 activating adjuvant.

[0247] P embodiment 7. The vaccine of P embodiment 6, wherein the SA antigen is covalently attached to the IL-17 activating adjuvant by a peptide linker.

[0248] P embodiment 8. The vaccine of any one of P embodiments 1 to 7, wherein the IL-17 activating adjuvant comprises CAF01, MPLA, TLR7, betaglucan, Curdlan, synthetic cord factor (TDB), diphtheria toxoid, pertussis toxoid, Poly IC, Flagellin from Salmonella typhimurium,Flagellin from vibrio cholera, PAM2CSK4, PAM3CSK4, a Bacterial CpG sequence, R484 (Resiquimod), Cholera toxin, or a combination thereof.

[0249] P embodiment 9. The vaccine of any one of P embodiments 1 to 8, further comprising alum.

[0250] P embodiment 10. The vaccine of P embodiment 8 or 9, wherein the IL-17 activating adjuvant comprises pertussis toxoid.

[0251] P embodiment 11. The vaccine of P embodiment 8 or 9, wherein the IL-17 activating adjuvant comprises CAF01.

[0252] P embodiment 12. The vaccine of P embodiment 8 or 9, wherein the IL-17 activating adjuvant comprises MPLA.

[0253] P embodiment 13. The vaccine of P embodiment 8 or 9, wherein the IL-17 activating adjuvant comprises TDB.

[0254] P embodiment 14. The vaccine of any one of P embodiments 1 to 9, wherein the SA antigen is IsdB and the IL-17 activating adjuvant is CAF01.

[0255] P embodiment 15. The vaccine of any one of P embodiments 1 to 9, wherein the SA antigen is IsdB, the IL-17 activating adjuvant is MPLA, and wherein the vaccine further comprises alum.

[0256] P embodiment 16. The vaccine of any one of P embodiments 1 to 9, wherein the SA antigen is IsdB, the IL-17 activating adjuvant is TDB, and wherein the vaccine further comprises alum.

[0257] P embodiment 17. The vaccine of any one of P embodiments 1 to 9, wherein the SA antigen is IsdB, the IL-17 activating adjuvant is pertussis toxoid, and wherein the SA antigen is attached to the IL-17 activating adjuvant.

[0258] P embodiment 18. The vaccine of any one of P embodiments 1 to 17, further comprising a pharmaceutical carrier.

[0259] P embodiment 19. A method of immunizing a subject from Staphylococcus aureus infection, comprising administering the vaccine of any one of P embodiments 1 to 17 to the subject.EMBODIMENTS

[0260] Embodiment 1. A vaccine comprising a non-toxin Staphylococcus aureus (SA) antigen and an IL-17 activating adjuvant.

[0261] Embodiment 2. The vaccine of Embodiment 1, wherein the IL-17 activating adjuvant activates IFN-γ.

[0262] Embodiment 3. The vaccine of Embodiment 1 or 2, wherein the non-toxin SA antigen is expressed on the surface of an SA bacteria.

[0263] Embodiment 4. The vaccine of any one of Embodiments 1 to 3, wherein the non-toxin SA antigen is covalently attached to the IL-17 activating adjuvant.

[0264] Embodiment 5. The vaccine of Embodiment 4, wherein the non-toxin SA antigen is covalently attached to the IL-17 activating adjuvant by a peptide linker.

[0265] Embodiment 6. The vaccine of any one of Embodiments 1 to 5, wherein the non-toxin SA antigen is iron-regulated surface determinant B (IsdB), iron-regulated surface determinant A (IsdA), manganese transport protein C (mntC), hydroxamate siderophore binding lipoprotein (FhuD2), serine-aspartate repeat protein E (sdrE), protein A (SpA), clumping factor A (clfA), Ess-secreted protein A (EsxA), Ess-secreted protein B (EsxB), clumping factor B (clfB), serine aspartate repeat protein D (SdrD), fibronectin binding protein A (FnBPA), fibronectin binding protein B (FnBPB), surface protein G (SasG), 5′-nucleotidase adenosine synthase A, surface protein X (SasX), surface protein C (SasC), coagulase, capsular polysaccharide 5 (CP5), capsular polysaccharide 8 (CP8), aureolysin (Aur), whole inactivated SA, Csa1, wall teichoic acid, lipoteichoic acid, glucosaminidase (Gmd), Staphylococcal binder of immunoglobulin (Sbi), extracellular fibrinogen-binding protein (Efb), nuclease (Nuc), extracellular adherence protein (Eap), serine-aspartate repeat-containing protein E (SdrE), serine-aspartate repeat-containing protein C (SdrC), collagen binding protein (Cna), or a combination thereof.

[0266] Embodiment 7. The vaccine of Embodiment 6, wherein the non-toxin SA antigen is IsdB, IsdA, mntC, FhuD2, sdrE, SpA, clfA, EsxA, EsxB, or a combination thereof.

[0267] Embodiment 8. The vaccine of Embodiment 7, wherein the non-toxin SA antigen is IsdB.

[0268] Embodiment 9. The vaccine of any one of Embodiments 1 to 8, further comprising a toxin SA antigen.

[0269] Embodiment 10. The vaccine of Embodiment 9, wherein the toxin SA antigen is α- hemolysin (Hla), toxic shock syndrome toxin (TSST), leukotoxin ED (LukED), protoxin subunit (LukS-PV), EsxAB toxin, Leukotoxin AB (LukAB), a phenol soluble modulin, or a combination thereof.

[0270] Embodiment 11. The vaccine of any one of Embodiments 1 to 8, wherein the vaccine does not comprise a toxin SA antigen.

[0271] Embodiment 12. The vaccine of any one of Embodiments 1 to 10, wherein the IL-17 activating adjuvant is CAF01, MPLA, a TLR7 agonist, betaglucan, Curdlan, synthetic cord factor (TDB), diphtheria toxoid, pertussis toxoid, Poly IC, Flagellin from Salmonella typhimurium, Flagellin from vibrio cholera, PAM2CSK4, PAM3CSK4, a CpG sequence, R484 (Resiquimod), Cholera toxin, ionomycin, phorbol 12-myristate 13-acetate (PMA), or a combination thereof.

[0272] Embodiment 13. The vaccine of Embodiment 12, wherein the IL-17 activating adjuvant is CAF01.

[0273] Embodiment 14. The vaccine of Embodiment 12, wherein the IL-17 activating adjuvant is MPLA.

[0274] Embodiment 15. The vaccine of Embodiment 12, wherein the IL-17 activating adjuvant is TDB.

[0275] Embodiment 16. The vaccine of Embodiment 12, wherein the IL-17 activating adjuvant is pertussis toxoid.

[0276] Embodiment 17. The vaccine of Embodiment 12, wherein the IL-17 activating adjuvant is diphtheria toxoid.

[0277] Embodiment 18. The vaccine of Embodiment 12, wherein the IL-17 activating adjuvant is ionomycin and PMA.

[0278] Embodiment 19. The vaccine of any one of Embodiments 1 to 12, wherein the non- toxin SA antigen is IsdB and the IL-17 activating adjuvant is CAF01.

[0279] Embodiment 20. The vaccine of any one of Embodiments 6 to 12, wherein the non- toxin SA antigen is IsdB, the IL-17 activating adjuvant is MPLA.

[0280] Embodiment 21. The vaccine of any one of Embodiments 1 to 12, wherein the non- toxin SA antigen is IsdB and the IL-17 activating adjuvant is TDB.

[0281] Embodiment 22. The vaccine of any one of Embodiments 1 to 12, wherein the non- toxin SA antigen is IsdB and the IL-17 activating adjuvant is pertussis toxoid.

[0282] Embodiment 23. The vaccine of any one of Embodiments 1 to 12, wherein the non- toxin SA antigen is IsdB and sdrE and the IL-17 activating adjuvant is CAF01.

[0283] Embodiment 24. The vaccine of any one of Embodiments 1 to 12, wherein the non- toxin SA antigen is IsdB and the IL-17 activating adjuvant is ionomycin and PMA.

[0284] Embodiment 25. The vaccine of any one of Embodiments 1 to 12, wherein the non- toxin SA antigen is MntC and the IL-17 activating adjuvant is CAF01.

[0285] Embodiment 26. The vaccine of any one of Embodiments 1 to 12, wherein the non- toxin SA antigen is IsdA and the IL-17 activating adjuvant is CAF01.

[0286] Embodiment 27. The vaccine of any one of Embodiments 1 to 12, wherein the non- toxin SA antigen is FhuD2 and the IL-17 activating adjuvant is CAF01.

[0287] Embodiment 28. The vaccine of any one of Embodiments 1 to 27, wherein the vaccine further comprises alum.

[0288] Embodiment 29. A pharmaceutical composition comprising a therapeutically or prophylactically effective amount of the vaccine of any one of Embodiments 1 to 28 and a pharmaceutically acceptable excipient.

[0289] Embodiment 30. A method of treating or preventing an SA-associated disease in a subject in need of such treatment or prevention, said method comprising administering a therapeutically or prophylactically effective amount of the vaccine of any one of Embodiments 1 to 27 to said subject.

[0290] Embodiment 31. The method of Embodiment 30, wherein said SA-associated disease is pneumonia, toxic shock syndrome, bloodstream infection, infective endocarditis, food poisoning, meningitis, an abscess, osteomyelitis, myositis, septic arthritis, a skin or soft tissue infection, or a combination thereof.

[0291] Embodiment 32. The method of Embodiment 30 or 31, wherein said subject was previously exposed to SA.

[0292] Embodiment 33. The method of Embodiment 32, wherein said subject was previously infected by SA.

[0293] Embodiment 34. The method of Embodiment 33, wherein the previous SA infection is a systemic infection.

[0294] Embodiment 35. The method of Embodiment 33, wherein the previous SA infection is a skin infection.

[0295] Embodiment 36. The method of any one of Embodiments 30 to 35, wherein said vaccine is administered intraperitoneally, intramuscularly, subcutaneously, intradermally, intranasally, or orally.

[0296] Embodiment 37. A method of immunizing a subject susceptible to SA infection, comprising administering to the subject the vaccine of any one of Embodiments 1 to 27.

[0297] Embodiment 38. The method of Embodiment 37, wherein said vaccine is administered under conditions such that antibodies directed to said non-toxin SA antigen or a functional fragment thereof are produced.

[0298] Embodiment 39. The method of Embodiment 38, wherein said antibodies are neutralizing antibodies.

[0299] Embodiment 40. The method of Embodiment 38 or 39, wherein said antibodies are IgG1 antibodies.

[0300] Embodiment 41. The method of any one of Embodiments 37 to 40, wherein said subject was previously exposed to SA.

[0301] Embodiment 42. The method of any one of Embodiments 37 to 40, wherein said subject was previously infected by SA.

[0302] Embodiment 43. The method of Embodiment 42, wherein the previous SA infection is a systemic infection.

[0303] Embodiment 44. The method of Embodiment 42, wherein the previous SA infection is a skin infection.

[0304] Embodiment 45. The method of any one of Embodiments 37 to 44, wherein said vaccine is administered intraperitoneally, intramuscularly, subcutaneously, intradermally, intranasally, or orally. EXAMPLES Example 1: Staphylococcus aureus vaccines including IL-17 activating adjuvants elicit protective immune responses

[0305] Staphylococcus aureus, besides being an opportunistic pathogen, frequently colonizes humans and leaves an immunosuppressive immune print that recapitulates upon vaccination with SA vaccines. Alum adjuvant has previously been employed for SA vaccines in human clinical trials. We hypothesized that the Alum adjuvant may not be the most effective adjuvant for SA vaccines and swapping alum with adjuvants that induce an immune response would improve effectiveness of vaccines. Humans are frequently colonized with SA; therefore, to mimic human conditions, we used a murine mice model that was previously exposed to SA followed by vaccination. To test our hypothesis, we employed several adjuvants along with the IsdB antigen. IsdB antigen is an iron-regulated surface determinant cell wall anchored protein used by SA for iron acquisition from host hemoglobin. The IsdB vaccine trial was a popular clinical trial that failed in 2013. We used IsdB antigen in our studies to demonstrate the effect of adjuvants on vaccine efficacy. Upon SA infection, we found downregulation of IL-17 responses and therefore, we hypothesized that boosting IL-17 responses at the time of vaccination might result in protective immunity against SA. Therefore, we used several IL-17-boosting adjuvants and showed the protective efficacy of the IsdB vaccine in our murine model.

[0306] We selected several adjuvants for improving the vaccine efficacy of the IsdB antigen in our prior exposure murine model. We selected adjuvants Alum, CAF01, MPLA, TLR7, betaglucan, Curdlan, synthetic cord factor (TDB), diphtheria toxoid and pertussis toxoid. Our results showed that CAF01+IsdB, MPLA+alum+IsdB, and TDB+alum+IsdB elicited protective immunity against SA, while adjuvants Alum+IsdB, beta-glucan+IsdB, curdlan+IsdB, beta- glucan+Alum+IsdB, and TDB+IsdB were non-protective. We demonstrated that the addition of TDB or MPLA to alum dramatically improved the adjuvant properties of Alum and the vaccine was highly effective against SA. We also showed that physically linking IsdB antigen to pertussis toxoid (Pertussis-IsdB fusion protein) but not to diphtheria toxoid (Diphtheria-IsdB fusion protein) elicited protective immunity against SA.

[0307] We have showed for the first time that replacing alum adjuvant with potent TH17- inducing adjuvants elicited efficient protection against SA. We first demonstrated the adjuvant effect on IsdB vaccine efficacy with CAF01 adjuvant, and also with the addition of TDB to alum adjuvant. Then, we demonstrated that the addition of MPLA to alum and physically linking IsdB antigen to pertussis-toxoid also elicited protective immunity against SA. To date, we showed that the CAF01+IsdB vaccine or MPLA or TDB+alum+IsdB antigen elicited potent antigen-specific protective T-cell responses, and the protection was dependent on IL-17 responses. Example 2: Staphylococcus aureus vaccines inhibit suppressive immune imprints

[0308] Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms relate to the difficulty of developing vaccines against pathobionts is unclear. Focusing on S. aureus (SA) that had resisted human vaccine development to date, herein, we show that non-protective CD4+T cell imprints link prior SA exposure to blunting of protective IsdB vaccine responses. CD4+T cell imprints express abundant IL-10 that is amplified by vaccination and drive inhibition of vaccine protection via IL-10Rα on CD4+T cell and IL-17A suppression. IL-10 further mediates cross-suppression of multi-antigen vaccines, but inefficiency of SA IsdB, IsdA and MntC vaccines could be overcome by IL-17A and IFN- ^ promoting adjuvancy. We propose that IL-10 secreting T cell imprints represent a major staphylococcal mechanism that needs to be overcome to generate protective vaccination.

[0309] Introduction

[0310] Pathobionts have maintained a long-standing relationship with the human host by negotiating coexistence through various immune evading strategies. Many pathobionts have to date proven to be elusive targets of vaccination. Notable among them are the ESK(C)APE (Enterococcus, Klebsiella, C. difficile, S. aureus, Acinetobacter, Pseudomonas and Enterobacter) pathogens for which no vaccines as of yet exist1,2. Likely, vaccinations against pathobionts need to overcome pathobiont`s immune evasive strategies to be successful3–6. Hence, for hard to generate vaccines, understanding of vaccine biology in the context of pathobiont`s immune evasion mechanisms may be required for the development of a successful vaccine.

[0311] SA is a pathobiont that colonizes and infects humans from early infancy, with up to fifty percent of infants having been exposed to SA by the age of 6 months7–10. SA is also a major opportunistic pathogen that has been the target of vaccine research effort since 1903, that has led to the development of a diverse list of seemingly effective vaccines11–13. Remarkably, for unclear reasons, none of these experimental vaccines have been successful in clinical trials14,15. Recently,we offered an explanation for the conundrum16. We posited that prior exposure to SA as routinely occurs in humans leads to immune imprints that somehow suppress subsequent vaccinations. Simulating the failed phase III SA vaccine trial that targeted staphylococcal iron- regulated surface determinant B (IsdB) antigen15, we showed that an IsdB vaccine that was otherwise protective in naïve mice, was ineffective when administered to mice previously infected with SA. We showed that SA infection induces largely non-protective humoral immune imprints that are preferentially recalled with IsdB vaccination, which thus leads to vaccine inefficacy. In that study, we demonstrated that non-neutralizing Fab and non-opsonic Fc domains were responsible for the ineffective antibody response16. However, fundamentally, it remains unclear how the pathobiont is able to induce broad non-protective imprints in the first place which subsequently drive the failure of vaccines. Hence, we set out to determine the pathobiont mechanism that underlies the development of non-protective imprints and subsequent vaccine suppression.

[0312] Results

[0313] SA induces suppressive CD4+T cell imprints that drive the loss of IsdB vaccine mediated T cell protection

[0314] Our prior study established the critical role of humoral immune imprints in IsdB vaccine interference16. Here, we investigated the impact immune imprints on protective T cell responses to IsdB vaccine adjuvanted with Alum (AIsdB). We used an established murine model16consisting of three intraperitoneal (i.p.) injections of SA LAC (USA300 strain) administered at a weekly interval. We then vaccinated the SA-exposed mice or naïve control mice weekly for three weeks, challenged the mice one week later, and then measured tissue SA burden 20 h later (FIG.5A).

[0315] First, to query the protective of role of T cells induced by AIsdB vaccination, we vaccinated B cell deficient (muMt-) mice and also performed adoptive CD3+T cell transfer from WT mice vaccinated with IsdB, then challenged the recipient mice with SA (FIG.s 5A-5C and FIG.s 11A-11C). Vaccination of naive muMt- mice with AlumIsdB (AIsdB) was protective against SA challenge (FIG.5B and FIG.11B), as was the adoptive transfer of total splenic CD3+T cells from naïve AIsdB vaccinated mice (FIG.5C and FIG.11C). Protection was notable in the spleen, kidney and peritoneum, and was augmented when tissue CFU burden was measured after 48 h of infection compared to 20 h (FIG.s 11D-11F), likely reflecting increased adaptive immune protection over time.

[0316] We investigated the CD3+T cell subset that conferred AIsdB vaccine protection by depleting T cell subsets using monoclo...

Claims

PATENT Attorney Docket No.: 048537-662001WO Client Ref. No. SD2024-044 WHAT IS CLAIMED IS:

1. A vaccine comprising a non-toxin Staphylococcus aureus (SA) antigen and an IL-17 activating adjuvant.

2. The vaccine of claim 1, wherein the IL-17 activating adjuvant activates IFN-γ.

3. The vaccine of claim 1, wherein the non-toxin SA antigen is a cell surface non-toxin SA antigen.

4. The vaccine of claim 1, wherein the non-toxin SA antigen is covalently attached to the IL-17 activating adjuvant.

5. The vaccine of claim 4, wherein the non-toxin SA antigen is covalently attached to the IL-17 activating adjuvant by a peptide linker.

6. The vaccine of claim 1, wherein the non-toxin SA antigen is iron- regulated surface determinant B (IsdB), iron-regulated surface determinant A (IsdA), manganese transport protein C (mntC), hydroxamate siderophore binding lipoprotein (FhuD2), serine- aspartate repeat protein E (sdrE), protein A (SpA), clumping factor A (clfA), Ess-secreted protein A (EsxA), Ess-secreted protein B (EsxB), clumping factor B (clfB), serine aspartate repeat protein D (SdrD), fibronectin binding protein A (FnBPA), fibronectin binding protein B (FnBPB), surface protein G (SasG), 5′-nucleotidase adenosine synthase A, surface protein X (SasX), surface protein C (SasC), coagulase, capsular polysaccharide 5 (CP5), capsular polysaccharide 8 (CP8), aureolysin (Aur), whole inactivated SA, Csa1, wall teichoic acid, lipoteichoic acid, glucosaminidase (Gmd), Staphylococcal binder of immunoglobulin (Sbi), extracellular fibrinogen-binding protein (Efb), nuclease (Nuc), extracellular adherence protein (Eap), serine-aspartate repeat-containing protein E (SdrE), serine-aspartate repeat-containing protein C (SdrC), collagen binding protein (Cna), or a combination thereof.PATENT Attorney Docket No.: 048537-662001WO Client Ref. No. SD2024-044 7. The vaccine of claim 6, wherein the non-toxin SA antigen is IsdB, IsdA, mntC, FhuD2, sdrE, SpA, clfA, EsxA, EsxB, or a combination thereof.

8. The vaccine of claim 7, wherein the non-toxin SA antigen is IsdB.

9. The vaccine of claim 1, further comprising a toxin SA antigen.

10. The vaccine of claim 9, wherein the toxin SA antigen is α-hemolysin (Hla), toxic shock syndrome toxin (TSST), leukotoxin ED (LukED), protoxin subunit (LukS- PV), Leukotoxin AB (LukAB), a phenol soluble modulin, or a combination thereof.

11. The vaccine of claim 1, wherein the vaccine does not comprise a toxin SA antigen.

12. The vaccine of claim 1, wherein the IL-17 activating adjuvant is CAF01, MPLA, a TLR7 agonist, betaglucan, Curdlan, synthetic cord factor (TDB), diphtheria toxoid, pertussis toxoid, Poly IC, Flagellin from Salmonella typhimurium, Flagellin from vibrio cholera, PAM2CSK4, PAM3CSK4, a CpG sequence, R484 (Resiquimod), Cholera toxin, ionomycin, phorbol 12-myristate 13-acetate (PMA), or a combination thereof.

13. The vaccine of claim 12, wherein the IL-17 activating adjuvant is CAF01.

14. The vaccine of claim 12, wherein the IL-17 activating adjuvant is MPLA.

15. The vaccine of claim 12, wherein the IL-17 activating adjuvant is TDB.

16. The vaccine of claim 12, wherein the IL-17 activating adjuvant is pertussis toxoid.

17. The vaccine of claim 12, wherein the IL-17 activating adjuvant is diphtheria toxoid.

18. The vaccine of claim 12, wherein the IL-17 activating adjuvant is ionomycin and PMA.

19. The vaccine of claim 1, wherein the non-toxin SA antigen is IsdB and the IL-17 activating adjuvant is CAF01.

20. The vaccine of claim 1, wherein the non-toxin SA antigen is IsdB, the IL- 17 activating adjuvant is MPLA.

21. The vaccine of claim 1, wherein the non-toxin SA antigen is IsdB and the IL-17 activating adjuvant is TDB.

22. The vaccine of claim 1, wherein the non-toxin SA antigen is IsdB and the IL-17 activating adjuvant is pertussis toxoid.

23. The vaccine of claim 1, wherein the non-toxin SA antigen is IsdB and sdrE and the IL-17 activating adjuvant is CAF01.

24. The vaccine of claim 1, wherein the non-toxin SA antigen is IsdB and the IL-17 activating adjuvant is ionomycin and PMA.

25. The vaccine of claim 1, wherein the non-toxin SA antigen is MntC and the IL-17 activating adjuvant is CAF01.

26. The vaccine of claim 1, wherein the non-toxin SA antigen is IsdA and the IL-17 activating adjuvant is CAF01.

27. The vaccine of claim 1, wherein the non-toxin SA antigen is FhuD2 and the IL-17 activating adjuvant is CAF01.

28. The vaccine of claim 1, wherein the vaccine further comprises alum.PATENT Attorney Docket No.: 048537-662001WO Client Ref. No. SD2024-044 29. A pharmaceutical composition comprising a therapeutically or prophylactically effective amount of the vaccine of claim 1 and a pharmaceutically acceptable excipient.

30. A method of treating or preventing an SA-associated disease in a subject in need of such treatment or prevention, said method comprising administering a therapeutically or prophylactically effective amount of the vaccine of claim 1 to said subject.

31. The method of claim 30, wherein said SA-associated disease is pneumonia, toxic shock syndrome, bloodstream infection, infective endocarditis, food poisoning, meningitis, an abscess, osteomyelitis, myositis, septic arthritis, a skin or soft tissue infection, or a combination thereof.

32. The method of claim 30, wherein said subject was previously exposed to SA.

33. The method of claim 32, wherein said subject was previously infected by SA.

34. The method of claim 33, wherein the previous SA infection is a systemic infection.

35. The method of claim 33, wherein the previous SA infection is a skin infection.

36. The method of claim 30, wherein said vaccine is administered intraperitoneally, intramuscularly, subcutaneously, intradermally, intranasally, or orally.

37. A method of immunizing a subject susceptible to SA infection, comprising administering to the subject the vaccine of claim 1.PATENT Attorney Docket No.: 048537-662001WO Client Ref. No. SD2024-044 38. The method of claim 37, wherein said vaccine is administered under conditions such that antibodies directed to said non-toxin SA antigen or a functional fragment thereof are produced.

39. The method of claim 38, wherein said antibodies are neutralizing antibodies.

40. The method of claim 38, wherein said antibodies are IgG1 antibodies.

41. The method of claim 37, wherein said subject was previously exposed to SA.

42. The method of claim 37, wherein said subject was previously infected by SA.

43. The method of claim 42, wherein the previous SA infection is a systemic infection.

44. The method of claim 42, wherein the previous SA infection is a skin infection.

45. The method of claim 37, wherein said vaccine is administered intraperitoneally, intramuscularly, subcutaneously, intradermally, intranasally, or orally.

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