Vaccination against helminth IL-33-modulators permits immune-mediated parasite ejection

The murine intestinal nematode Heligmosomoides polygyrus bakeri powerfully modulates the host immune response. This is achieved in part through the HpARI family (HpARI1/2/3), which act on IL-33, and the HpBARI family (HpBARI and HpBARI_Hom2), which act on ST2. Here, we find that this immunomodulation is evident only in the first week of infection, with abrogation of ST2 detection and systemic suppression of IL-33-dependent responses. Vaccination with individual HpARI or HpBARI family members raised antibody responses which could block these proteins’ immunomodulatory activities. During infection, vaccination could release the host from immunosuppression: HpARI2 vaccination resulted in much increased ILC2 and Th2 immunity, with heightened serum IL-4 and IL-5 responses, but did not abrogate ST2 suppression. In contrast, a HpBARI+HpBARI_Hom2 vaccination cocktail resulted in abrogation of ST2 suppression, and again increased Th2 immunity and serum cytokine responses. Either of the HpARI2 or the HpBARI cocktail vaccinations provided significant protection against subsequent H. polygyrus bakeri infection. We therefore show a proof of principle that vaccination with immunomodulatory proteins can protect the host against infection, and can be used as a tool for blocking the effects of specific parasite-derived proteins.