Type 2 immune-inducing helminth vaccination maintains protective efficacy in the setting of repeated parasite exposures

Animal studies have demonstrated that helminth vaccines which induce type 2 immune responses can be protective. To date, however, such vaccines have not been tested against repeated parasite challenges. Since repeated antigenic challenge of patients with allergic disease results in immunologic tolerance, we hypothesized that a helminth vaccine which induces type 2 immune responses may lose its protective efficacy in the setting of repeated parasite exposures (RPEs). To test this hypothesis, we examined whether RPEs induce immunological tolerance and reduce the effectiveness of a type 2 immune-inducing vaccine. BALB/c mice vaccinated against Litomosoides sigmodontis, a filarial nematode of rodents, were repeatedly exposed to irradiated larvae for 2 or 8 weeks or to non-irradiated infectious larvae for three months. Vaccination-induced parasite-specific IgE levels, parasite antigen-driven basophil interleukin 4 (IL-4) release, and Th2 skewing of the cellular immune response remained stable in the face of RPEs. Furthermore, RPEs in vaccinated mice did not augment immunoregulatory responses, as parasite antigen-driven cellular proliferation, production of IL-10, and frequencies of CD4⁺CD25⁺FoxP3⁺ regulatory T-cells were not altered by RPEs. Challenge infections with infectious L3-stage larvae resulted in lower worm burdens in vaccinated mice given RPEs than in vaccinated controls. These results demonstrate that vaccines which induce type 2 immune responses can maintain their efficacy in the setting of repeated parasite exposures.