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Comparison of Intranasal Outer Membrane Vesicles with Cholera Toxin and Injected MF59C.1 as Adjuvants for Malaria Transmission Blocking Antigens AnAPN1 and Pfs48/45.

Pritsch M, Ben-Khaled N, Chaloupka M, Kobold S, Berens-Riha N, Peter A, Liegl G, Schubert S, Hoelscher M, Löscher T, Wieser A - J Immunol Res (2016)

Bottom Line: Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3) were measured by ELISA.T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells) were determined by flow cytometry.Antigen-specific IgG titres above 1 : 10(5) could be detected in all groups.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), 80802 Munich, Germany; Department of Bacteriology, Max von Pettenkofer Institute (LMU), 81337 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, 80802 Munich, Germany.

ABSTRACT
Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV) are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice. The intranasal adjuvant cholera toxin (CT) and parenteral adjuvant MF59C.1 were used in comparison. Vaccinations were administered intranasally or subcutaneously. Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3) were measured by ELISA. T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells) were determined by flow cytometry. When OMV were used as adjuvant for intranasal immunization, antibody and cellular responses against all three antigens could be induced, comparable to cholera toxin and MF59C.1. Antigen-specific IgG titres above 1 : 10(5) could be detected in all groups. This study provides the rationale for further development of OMV as a vaccination strategy in malaria and other diseases.

No MeSH data available.


Related in: MedlinePlus

Characterization of the cellular response to AnAPN1 vaccination. Each dot or triangle represents an individual mouse. Each PBS vaccination consisted of four mice and each AnAPN1 vaccination group of five mice. Comparisons between groups were performed by Student's t-test. (a) Percentage of IFN-g secreting CD3 and CD8 double positive cells. (b) Percentage of IFN-g secreting CD3 and CD4 double positive cells. (c) Percentage of IL-17 secreting CD3 and CD4 double positive cells. (d) Percentage of Foxp3 positive CD3 and CD4 double positive cells. NS = nonsignificant; ∗ = significant difference p < 0.05; OMVs = bacterial outer membrane vesicles; CT = cholera toxin; ND = not determined.
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fig5: Characterization of the cellular response to AnAPN1 vaccination. Each dot or triangle represents an individual mouse. Each PBS vaccination consisted of four mice and each AnAPN1 vaccination group of five mice. Comparisons between groups were performed by Student's t-test. (a) Percentage of IFN-g secreting CD3 and CD8 double positive cells. (b) Percentage of IFN-g secreting CD3 and CD4 double positive cells. (c) Percentage of IL-17 secreting CD3 and CD4 double positive cells. (d) Percentage of Foxp3 positive CD3 and CD4 double positive cells. NS = nonsignificant; ∗ = significant difference p < 0.05; OMVs = bacterial outer membrane vesicles; CT = cholera toxin; ND = not determined.

Mentions: In contrast, when comparing the ability of the said adjuvants to induce AnAPN1-specific cellular responses, only OMV was able to induce a cytotoxic T cell response towards AnAPN1, but all induced a Th1 response towards the antigen (Figures 5(a) and 5(b)). Again, no induction of antigen-specific Th17 or regulatory T cells (Figures 5(c) and 5(d)) could be observed.


Comparison of Intranasal Outer Membrane Vesicles with Cholera Toxin and Injected MF59C.1 as Adjuvants for Malaria Transmission Blocking Antigens AnAPN1 and Pfs48/45.

Pritsch M, Ben-Khaled N, Chaloupka M, Kobold S, Berens-Riha N, Peter A, Liegl G, Schubert S, Hoelscher M, Löscher T, Wieser A - J Immunol Res (2016)

Characterization of the cellular response to AnAPN1 vaccination. Each dot or triangle represents an individual mouse. Each PBS vaccination consisted of four mice and each AnAPN1 vaccination group of five mice. Comparisons between groups were performed by Student's t-test. (a) Percentage of IFN-g secreting CD3 and CD8 double positive cells. (b) Percentage of IFN-g secreting CD3 and CD4 double positive cells. (c) Percentage of IL-17 secreting CD3 and CD4 double positive cells. (d) Percentage of Foxp3 positive CD3 and CD4 double positive cells. NS = nonsignificant; ∗ = significant difference p < 0.05; OMVs = bacterial outer membrane vesicles; CT = cholera toxin; ND = not determined.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4863099&req=5

fig5: Characterization of the cellular response to AnAPN1 vaccination. Each dot or triangle represents an individual mouse. Each PBS vaccination consisted of four mice and each AnAPN1 vaccination group of five mice. Comparisons between groups were performed by Student's t-test. (a) Percentage of IFN-g secreting CD3 and CD8 double positive cells. (b) Percentage of IFN-g secreting CD3 and CD4 double positive cells. (c) Percentage of IL-17 secreting CD3 and CD4 double positive cells. (d) Percentage of Foxp3 positive CD3 and CD4 double positive cells. NS = nonsignificant; ∗ = significant difference p < 0.05; OMVs = bacterial outer membrane vesicles; CT = cholera toxin; ND = not determined.
Mentions: In contrast, when comparing the ability of the said adjuvants to induce AnAPN1-specific cellular responses, only OMV was able to induce a cytotoxic T cell response towards AnAPN1, but all induced a Th1 response towards the antigen (Figures 5(a) and 5(b)). Again, no induction of antigen-specific Th17 or regulatory T cells (Figures 5(c) and 5(d)) could be observed.

Bottom Line: Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3) were measured by ELISA.T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells) were determined by flow cytometry.Antigen-specific IgG titres above 1 : 10(5) could be detected in all groups.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), 80802 Munich, Germany; Department of Bacteriology, Max von Pettenkofer Institute (LMU), 81337 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, 80802 Munich, Germany.

ABSTRACT
Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV) are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice. The intranasal adjuvant cholera toxin (CT) and parenteral adjuvant MF59C.1 were used in comparison. Vaccinations were administered intranasally or subcutaneously. Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3) were measured by ELISA. T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells) were determined by flow cytometry. When OMV were used as adjuvant for intranasal immunization, antibody and cellular responses against all three antigens could be induced, comparable to cholera toxin and MF59C.1. Antigen-specific IgG titres above 1 : 10(5) could be detected in all groups. This study provides the rationale for further development of OMV as a vaccination strategy in malaria and other diseases.

No MeSH data available.


Related in: MedlinePlus