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Vaccines

Schistosoma mansoni Soluble Egg Antigens Enhance Listeria monocytogenes Vector HIV-1 Vaccine Induction of Cytotoxic T Cells

Cac T. Bui, Lisa M. Shollenberger, Yvonne Paterson, Donald A. Harn
P. P. Wilkins, Editor
Cac T. Bui
aDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
bCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA
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Lisa M. Shollenberger
aDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
bCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA
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Yvonne Paterson
cDepartment of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Donald A. Harn
aDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
bCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA
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P. P. Wilkins
Roles: Editor
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DOI: 10.1128/CVI.00138-14
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    FIG 1

    SEA enhances vaccine-specific IFN-γ-producing Th1 and CTLs. Splenocytes from naive and vaccinated mice were collected 2 wplv and immune responses to the immunodominant HIV Gag CD4+ helper (A) and CTL epitopes for HIV Gag (B) and LLO (C) were analyzed by IFN-γ ELISpot. Data were pooled from two similar, independent experiments and results from individual mice (n = 16) were plotted. Statistical analysis was performed using one-way ANOVA with Newman Keuls post hoc test. **, P < 0.01; ***, P < 0.001; ns, not significant.

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    FIG 2

    SEA augments functional CTL response of vaccinated mice in vivo. Naive splenocytes were stained with CFSE at low and high concentrations and then pulsed with an irrelevant or immunodominant CTL epitope of HIV Gag, respectively. These targets were injected into naive or vaccinated mice. After 18 h, splenocytes were collected and analyzed for specific killing of targets using flow cytometry. (A) Representative histograms of irrelevant (left peak) and HIV Gag (right peak) targets recovered from each animal group are shown. (B) Representative data from three independent experiments are shown. Levels of specific killing in individual mice (n = 8) were plotted and the groups were compared by one-way ANOVA and Newman-Keuls post hoc test. ***, P < 0.001.

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    FIG 3

    SEA increases multiple T cell populations when coadministered with Lm-Gag vaccine. Splenocytes from naive and vaccinated mice were collected 2 wplv and assayed by flow cytometry for Th1 (A), Th2 (B), Th17 (C), and Tregs (D and E) or IFN-γ-secreting CTLs (F). Percentages of each T cell population from individual mice (n = 8) were plotted and statistical differences between groups were analyzed by one-way ANOVA and Newman-Keuls post hoc test. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant.

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    FIG 4

    SEA increases vaccine-specific proinflammatory cytokine production in vaccinated mice. Splenocytes from naive and vaccinated mice were collected 2 wplv and stimulated with immunodominant CD4+ helper (square) and CTL epitopes for HIV Gag (circle) and LLO (triangle) for 72 h. Unstimulated controls (open circle) were included for each treatment. Cytokine production levels in supernatants were quantified by CBA. Statistical analysis was performed using two-way ANOVA with Bonferroni post hoc test. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.

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    FIG 5

    SEA improves longevity of vaccine-specific Th1 and CTL responses. Splenocytes from each animal group were collected at 12 (open symbols) and 20 wplv (filled symbols) and immune response to the immunodominant CD4+ helper (A) and CTL epitopes for HIV Gag (B) and LLO (C) were assayed by IFN-γ ELISpot. Data were pooled from two similar, independent experiments and results from individual mice (n = 8) were plotted. Statistical analysis was performed using one-way ANOVA with Newman Keuls post hoc test. *, P < 0.05; ***, P < 0.001.

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    Files in this Data Supplement:

    • Supplemental file 1 -

      Fig. S1. SEA alone does not induce Gag-specific CTL or T helper 1 responses. Fig. S2. SEA does not affect vaccine-specific IL-4-producing Th2 response. Fig. S3. SEA coadministration does not induce vaccine-specific Th2 or Th17 cytokine production in mice. Fig. S4. SEA/Lm-Gag-vaccinated mice promote a mixed Th1/Th2 cytokine profile upon SEA restimulation.

      PDF, 274K

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Schistosoma mansoni Soluble Egg Antigens Enhance Listeria monocytogenes Vector HIV-1 Vaccine Induction of Cytotoxic T Cells
Cac T. Bui, Lisa M. Shollenberger, Yvonne Paterson, Donald A. Harn
Clinical and Vaccine Immunology Aug 2014, 21 (9) 1232-1239; DOI: 10.1128/CVI.00138-14

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Schistosoma mansoni Soluble Egg Antigens Enhance Listeria monocytogenes Vector HIV-1 Vaccine Induction of Cytotoxic T Cells
Cac T. Bui, Lisa M. Shollenberger, Yvonne Paterson, Donald A. Harn
Clinical and Vaccine Immunology Aug 2014, 21 (9) 1232-1239; DOI: 10.1128/CVI.00138-14
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