Adjuvant selection for vaccination against murine schistosomiasis

Schistosoma mansoni cercariae penetrate mouse epidermis, detach the glycocalyx and transform into schistosomula, triggering innate immune responses by host keratinocytes and Langerhans cells. Schistosomula leave the dermis and enter blood capillaries, releasing excretory/secretory products (ESP), which induce readily detectable primary adaptive immunity responses, dominated by T helper (Th) 1 and 17 cytokines. Partial protection against murine schistosomiasis may be achieved using subunit antigens and Th1 cytokine-inducing adjuvants. Conversely, resistance to primary and/or secondary schistosomiasis in rats, mice and humans is associated with production of Th2 cytokines. Accordingly, we reasoned that effective vaccination against murine primary schistosomiasis might be achieved provided selection of an adjuvant capable of skewing the S. mansoni larval ESP-mediated Th1/Th17 immune responses towards a Th2 profile. In an aim to select such an adjuvant, we administered the prototypical Th1 and Th2, respectively, C57BL/6 and BALB/c mice with polyinosinic-polycytidylic acid (Poly I/C), peptidoglycan (PGN), or thymic stromal lymphopoietin (TSLP) before exposure to S. mansoni cercariae. Serum antibody reactivity and ex vivo spleen cells (SC) immune responses to larval ESP, in a recombinant or multiple antigen peptide form, were assessed 1 week after infection. Injection with Poly I/C failed to increase interleukin (IL)-4 and led to elevated gamma interferon (IFN-γ) levels released by unstimulated or ESP-stimulated SC. Treatment with PGN triggered hightened amounts of IL-4, IL-17 and IFN-γ released by unstimulated or ESP-stimulated C57BL/6 SC. In contrast, TSLP succeeded in directing the ESP-mediated immune responses towards a Th2-biased profile in prototypical Th1 and Th2 mice.