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Clinical Trial
. 2001 Mar;69(3):1574-80.
doi: 10.1128/IAI.69.3.1574-1580.2001.

Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR

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Clinical Trial

Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR

P J Cooper et al. Infect Immun. 2001 Mar.

Abstract

To investigate the potential immunomodulatory effects of concurrent ascariasis on the cytokine response to a live oral vaccine, we measured cytokine responses to cholera toxin B subunit (CT-B) following vaccination with the live oral cholera vaccine CVD 103-HgR in Ascaris lumbricoides-infected subjects randomized in a double-blind study to receive two doses of either albendazole or placebo prior to vaccination and in a group of healthy U.S. controls. Postvaccination cytokine responses to CT-B were characterized by transient increases in the production of interleukin-2 (IL-2; P = 0.02) and gamma interferon (IFN-gamma; P = 0.001) in the three study groups combined; however, postvaccination increases in IFN-gamma were significant only in the albendazole-treated A. lumbricoides infection group (P = 0.008). Postvaccination levels of IL-2 were significantly greater in the albendazole-treated group compared with the placebo group (P = 0.03). No changes in levels of Th1 and Th2 cytokines in response to control ascaris antigens were observed over the same period. These findings indicate that vaccination with CVD 103-HgR is associated with a Th1 cytokine response (IL-2 and IFN-gamma) to CT-B, that infection with A. lumbricoides diminishes the magnitude of this response, and that albendazole treatment prior to vaccination was able to partially reverse the deficit in IL-2. The potential modulation of the immune response to oral vaccines by geohelminth parasites has important implications for the design of vaccination campaigns in geohelminth-endemic areas.

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Figures

FIG. 1
FIG. 1
Lymphoproliferative, IFN-γ cytokine, and ASC responses to CT-B in eight healthy controls following vaccination with CVD 103-HgR. (A) Percent change of stimulation indices (SI) compared with prevaccination levels. (B) IFN-γ production. (C) CT-B-specific ASC frequencies. Box plots represent median values (central line), interquartile range (box margins), 95% confidence intervals (bars), and outlying values (circles). The observation times at which median values were significantly greater (P < 0.05) than prevaccination levels are indicated (∗). Numbers within or above boxes show the proportions (percentages) of subjects with a detectable response for each group.
FIG. 2
FIG. 2
Production of cytokines IL-2, IFN-γ, and IL-5 by PBMC stimulated with CT-B in the Ecuador study groups. Young adults with ascariasis were randomized to receive two sequential doses (days −37 and −7) of either albendazole (400 mg) or placebo, after which all received a single dose of CVD 103-HgR (day 0). PBMC were stimulated with CT-B at day −37 prevaccination, day 0, and days 14 and 28 postvaccination. Shown are box plots of net cytokine production. The observation times at which median values were significantly greater (P < 0.05) than prevaccination levels are shown (+). Times at which intergroup differences were significant (P < 0.05) are shown also (∗). Numbers within or above boxes show the proportions (percentages) of subjects with a detectable response for each group.
FIG. 3
FIG. 3
Production of cytokines IL-2, IFN-γ, and IL-5 by PBMC stimulated with L2/L3 ascaris antigen in the Ecuador study groups. Shown are box plots of net cytokine production at the study times described in Fig. 2. There were no significant inter- or intragroup differences over the study period for any of the three cytokines. Numbers within or above boxes show the proportions (percentages) of subjects with a detectable response for each group.

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