Schistosomiasis vaccine SchistoShield® induces functional immune memory responses in US and African populations

Helminth parasites of the genus Schistosoma cause 290,000 deaths annually, mostly in tropical and subtropical regions. An estimated 250 million people are currently chronically infected with Schistosoma parasites, imposing a risk of new and recurrent infections in an additional 800 million people. SchistoShield^® (Sm-p80 + GLA-SE) is a leading vaccine candidate for schistosomiasis that has successfully completed Phase 1 (USA) and Phase 1b (Africa) safety and immunogenicity clinical trials. Using Peripheral Blood Mononuclear Cells (PBMCs) obtained from intercontinental Phase 1 and Phase 1b trial participants, adaptive immune effector and memory responses to SchistoShield^® were investigated. Functional recall responses were measured in vitro using Sm-p80 vaccine antigen. Results clearly demonstrate that the vaccine induced pronounced effector and memory T-cell responses. Upon recall with Sm-p80 antigen, cytokines including IFN-γ, TNF-α, IL-17A, IL-9, and granzyme B were produced, indicating the generation of functionally heterogeneous CD4 T-helper and cytotoxic lymphocyte responses. Consistent with T-helper responses that promote humoral immunity, Sm-p80 antigen-specific antibody-secreting plasmablasts were detected in vaccinated volunteers who were tracked longitudinally. Taken together, the SchistoShield® vaccine induced robust cell-mediated effector and memory responses, hallmarks of a potentially efficacious vaccine against schistosome/helminth parasites.