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Evaluation of the protective immunity of a novel subunit fusion vaccine in a murine model of systemic MRSA infection.

Zuo QF, Yang LY, Feng Q, Lu DS, Dong YD, Cai CZ, Wu Y, Guo Y, Gu J, Zeng H, Zou QM - PLoS ONE (2013)

Bottom Line: Immunization with the chimeric bivalent vaccine induced strong antibody and T cell responses.When the protective efficacy of the chimeric bivalent vaccine was compared to that of individual proteins in a murine model of systemic S. aureus infection, the bivalent vaccine showed a stronger protective immune response than the individual proteins (IsdB or Hla).Based on the results presented here, the chimeric bivalent vaccine affords higher levels of protection against S. aureus and has potential as a more effective candidate vaccine.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, The Third Military Medical University, Chongqing, People's Republic of China.

ABSTRACT
Staphylococcus aureus is a common commensal organism in humans and a major cause of bacteremia and hospital acquired infection. Because of the spread of strains resistant to antibiotics, these infections are becoming more difficult to treat. Therefore, exploration of anti-staphylococcal vaccines is currently a high priority. Iron surface determinant B (IsdB) is an iron-regulated cell wall-anchored surface protein of S. aureus. Alpha-toxin (Hla) is a secreted cytolytic pore-forming toxin. Previous studies reported that immunization with IsdB or Hla protected animals against S. aureus infection. To develop a broadly protective vaccine, we constructed chimeric vaccines based on IsdB and Hla. Immunization with the chimeric bivalent vaccine induced strong antibody and T cell responses. When the protective efficacy of the chimeric bivalent vaccine was compared to that of individual proteins in a murine model of systemic S. aureus infection, the bivalent vaccine showed a stronger protective immune response than the individual proteins (IsdB or Hla). Based on the results presented here, the chimeric bivalent vaccine affords higher levels of protection against S. aureus and has potential as a more effective candidate vaccine.

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Recombinant antigen vaccines administered with alum adjuvant prime murine spleen cells for cytokine responses.One week following the last booster, spleen cells of mice (n = 6) immunized with antigen-free PBS and alum adjuvant or from mice immunized with recombinant proteins (IsdB, Hla, HI, IH) were incubated for 5 days with antigen proteins (5 µg/ml). The supernatants were harvested, and the cytokine levels of (A) IFN-γ, (B) IL-5, and (C) IL-17A were determined. The medians and interquartile ranges are shown. Asterisks indicate significant differences between the vaccinated and control mice (* P<0.05, ** P<0.01). (D) Role of cytokines in splenocyte supernatants after 5 days of co-culture with recombinant proteins in the phagocytic killing of staphylococci. PMNs were primed with supernatants for four hours, and S. aureus (1:10 S. aureus to PMNs) was added for an additional ninety minute incubation period. The bacteria were then plated on agar medium to measure the bacterial survival as CFU. The medians and interquartile ranges are shown. Asterisks indicate significant differences between the immune and control supernatants (* P<0.05, ** P<0.01).
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pone-0081212-g005: Recombinant antigen vaccines administered with alum adjuvant prime murine spleen cells for cytokine responses.One week following the last booster, spleen cells of mice (n = 6) immunized with antigen-free PBS and alum adjuvant or from mice immunized with recombinant proteins (IsdB, Hla, HI, IH) were incubated for 5 days with antigen proteins (5 µg/ml). The supernatants were harvested, and the cytokine levels of (A) IFN-γ, (B) IL-5, and (C) IL-17A were determined. The medians and interquartile ranges are shown. Asterisks indicate significant differences between the vaccinated and control mice (* P<0.05, ** P<0.01). (D) Role of cytokines in splenocyte supernatants after 5 days of co-culture with recombinant proteins in the phagocytic killing of staphylococci. PMNs were primed with supernatants for four hours, and S. aureus (1:10 S. aureus to PMNs) was added for an additional ninety minute incubation period. The bacteria were then plated on agar medium to measure the bacterial survival as CFU. The medians and interquartile ranges are shown. Asterisks indicate significant differences between the immune and control supernatants (* P<0.05, ** P<0.01).

Mentions: To investigate the cytokine profiles in the spleen cells of mice immunized with recombinant proteins and control mice immunized with alum adjuvant one week after the last booster, spleen cells from all of the groups were stimulated with the recombinant proteins for 5 days, and cytokine production was analyzed in the supernatants. The splenocytes from vaccinated mice (IsdB, Hla, HI, IH) produced significantly more IFN-γ (Figure 5A) (IsdB, P = 0.0043; HI, P = 0.0087; IH, P = 0.0043), IL-5 (Figure 5B) (IsdB, P = 0.0154; HI, P = 0.0048; IH, P = 0.0048), and IL-17A (Figure 5C) (IsdB, P = 0.0152; Hla, P = 0.02; HI, P = 0.0022; IH, P = 0.0050) in response to the recombinant proteins IsdB, Hla, HI or IH than did splenocytes from control mice. Further, the splenocytes from vaccinated mice (HI, IH) produced significantly more IFN-γ (Figure 5A) (HI, P = 0.0411; IH, P = 0.0411), IL-5 (Figure 5B) (HI, P = 0.0087; IH, P = 0.0087), and IL-17A (Figure 5C) (HI, P = 0.0043; IH, P = 0.0412) in response to the recombinant proteins HI or IH than did splenocytes from control mice who had received IsdB.


Evaluation of the protective immunity of a novel subunit fusion vaccine in a murine model of systemic MRSA infection.

Zuo QF, Yang LY, Feng Q, Lu DS, Dong YD, Cai CZ, Wu Y, Guo Y, Gu J, Zeng H, Zou QM - PLoS ONE (2013)

Recombinant antigen vaccines administered with alum adjuvant prime murine spleen cells for cytokine responses.One week following the last booster, spleen cells of mice (n = 6) immunized with antigen-free PBS and alum adjuvant or from mice immunized with recombinant proteins (IsdB, Hla, HI, IH) were incubated for 5 days with antigen proteins (5 µg/ml). The supernatants were harvested, and the cytokine levels of (A) IFN-γ, (B) IL-5, and (C) IL-17A were determined. The medians and interquartile ranges are shown. Asterisks indicate significant differences between the vaccinated and control mice (* P<0.05, ** P<0.01). (D) Role of cytokines in splenocyte supernatants after 5 days of co-culture with recombinant proteins in the phagocytic killing of staphylococci. PMNs were primed with supernatants for four hours, and S. aureus (1:10 S. aureus to PMNs) was added for an additional ninety minute incubation period. The bacteria were then plated on agar medium to measure the bacterial survival as CFU. The medians and interquartile ranges are shown. Asterisks indicate significant differences between the immune and control supernatants (* P<0.05, ** P<0.01).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3852261&req=5

pone-0081212-g005: Recombinant antigen vaccines administered with alum adjuvant prime murine spleen cells for cytokine responses.One week following the last booster, spleen cells of mice (n = 6) immunized with antigen-free PBS and alum adjuvant or from mice immunized with recombinant proteins (IsdB, Hla, HI, IH) were incubated for 5 days with antigen proteins (5 µg/ml). The supernatants were harvested, and the cytokine levels of (A) IFN-γ, (B) IL-5, and (C) IL-17A were determined. The medians and interquartile ranges are shown. Asterisks indicate significant differences between the vaccinated and control mice (* P<0.05, ** P<0.01). (D) Role of cytokines in splenocyte supernatants after 5 days of co-culture with recombinant proteins in the phagocytic killing of staphylococci. PMNs were primed with supernatants for four hours, and S. aureus (1:10 S. aureus to PMNs) was added for an additional ninety minute incubation period. The bacteria were then plated on agar medium to measure the bacterial survival as CFU. The medians and interquartile ranges are shown. Asterisks indicate significant differences between the immune and control supernatants (* P<0.05, ** P<0.01).
Mentions: To investigate the cytokine profiles in the spleen cells of mice immunized with recombinant proteins and control mice immunized with alum adjuvant one week after the last booster, spleen cells from all of the groups were stimulated with the recombinant proteins for 5 days, and cytokine production was analyzed in the supernatants. The splenocytes from vaccinated mice (IsdB, Hla, HI, IH) produced significantly more IFN-γ (Figure 5A) (IsdB, P = 0.0043; HI, P = 0.0087; IH, P = 0.0043), IL-5 (Figure 5B) (IsdB, P = 0.0154; HI, P = 0.0048; IH, P = 0.0048), and IL-17A (Figure 5C) (IsdB, P = 0.0152; Hla, P = 0.02; HI, P = 0.0022; IH, P = 0.0050) in response to the recombinant proteins IsdB, Hla, HI or IH than did splenocytes from control mice. Further, the splenocytes from vaccinated mice (HI, IH) produced significantly more IFN-γ (Figure 5A) (HI, P = 0.0411; IH, P = 0.0411), IL-5 (Figure 5B) (HI, P = 0.0087; IH, P = 0.0087), and IL-17A (Figure 5C) (HI, P = 0.0043; IH, P = 0.0412) in response to the recombinant proteins HI or IH than did splenocytes from control mice who had received IsdB.

Bottom Line: Immunization with the chimeric bivalent vaccine induced strong antibody and T cell responses.When the protective efficacy of the chimeric bivalent vaccine was compared to that of individual proteins in a murine model of systemic S. aureus infection, the bivalent vaccine showed a stronger protective immune response than the individual proteins (IsdB or Hla).Based on the results presented here, the chimeric bivalent vaccine affords higher levels of protection against S. aureus and has potential as a more effective candidate vaccine.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, The Third Military Medical University, Chongqing, People's Republic of China.

ABSTRACT
Staphylococcus aureus is a common commensal organism in humans and a major cause of bacteremia and hospital acquired infection. Because of the spread of strains resistant to antibiotics, these infections are becoming more difficult to treat. Therefore, exploration of anti-staphylococcal vaccines is currently a high priority. Iron surface determinant B (IsdB) is an iron-regulated cell wall-anchored surface protein of S. aureus. Alpha-toxin (Hla) is a secreted cytolytic pore-forming toxin. Previous studies reported that immunization with IsdB or Hla protected animals against S. aureus infection. To develop a broadly protective vaccine, we constructed chimeric vaccines based on IsdB and Hla. Immunization with the chimeric bivalent vaccine induced strong antibody and T cell responses. When the protective efficacy of the chimeric bivalent vaccine was compared to that of individual proteins in a murine model of systemic S. aureus infection, the bivalent vaccine showed a stronger protective immune response than the individual proteins (IsdB or Hla). Based on the results presented here, the chimeric bivalent vaccine affords higher levels of protection against S. aureus and has potential as a more effective candidate vaccine.

Show MeSH
Related in: MedlinePlus