Human Infection withAscaris lumbricoidesIs 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

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-␥; P ‫؍‬ 0.001) in the three study groups combined; however, postvaccination increases in IFN-␥ 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-␥) 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.

Low dose chronicSchistosoma mansoniinfection increases susceptibility toMycobacterium bovisBCG infection in mice

“…In mice with established S. mansoni infection, immunization with sperm whale myoglobin induces antigen-specific T cells that produce Th2 cytokines, whereas uninfected animals generate Th1 type immunity [14]. Helminth infections were also reported to impair resistance against viral infections [5] and reduce cellular responses generated by vaccinations against viral pathogens [15]. Although the interaction between helminth and mycobacterial infections has not been studied, mice immunized with PPD following the induction of strong Th2 responses by filarial worm Brugia malayi were found to develop T cell cytokine responses that were polarized towards type 2 pattern [6].…”

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

“…During a placebo-controlled trial among 6-13 year-old children in Ecuador who were infected with Ascaris lumbricoides, two doses of albendazole (an anthelmintic) prompted a modest improvement in immunogenicity following a subsequent dose of CVD 103-HgR [92], though seroconversion rates in albendazole-treated children (∼30%) still fell considerably short of those observed in North-American adults (>90%) [139]. A subsequent trial in Ecuadorian teenagers revealed that A. lumbricoides inhibits Th1 cytokine responses (including IL-2 and IFN-γ) to CVD 103-HgR, and that albendazole treatment prior to vaccination partly reverses these effects [128]. However, deworming did not yield similar benefits for the immunogenicity of inactivated cholera vaccine among children in Bangladesh or Gabon [140,141].…”

“…A subsequent trial in Ecuadorian teenagers revealed that A. lumbricoides inhibits Th1 cytokine responses (including IL-2 and IFN-γ) to CVD 103-HgR, and that albendazole treatment prior to vaccination partly reverses these effects [128]. However, deworming did not yield similar benefits for the immunogenicity of inactivated cholera vaccine among children in Bangladesh or Gabon [140,141].…”

“…In particular, type I, II and III interferons induced by viral or bacterial pathogens may inhibit vaccine virus replication and immunogenicity through a number of mechanisms including direct antiviral activity, innate immune cell activation and regulation of adaptive immune responses [125,126]. Other immunomodulatory effects may be pertinent, such as the suppression of Th1 cytokine production by intestinal helminths [127,128], the promotion of mucosal tolerance via the induction of regulatory T cells or the functional reprogramming of innate immune cells that protects against subsequent colonization (trained immunity) [129]. The inhibitory effect of non-polio enteroviruses (NPEVs) on OPV is perhaps the most robust association to be demonstrated between a group of enteric pathogens and an oral vaccine.…”

Boosting the suppressive effects of Ascaris suum components in IFN-γ-deficient mice

“…Ascaris species are similar in their capacity to suppress the protective immune response of the host 4 . In this regard, our results show that PI impaired the IL-12p40-mediated neutrophilic influx.…”