Controlled human helminth infection models: insights into type 2 immunity and therapeutic development

Controlled human infection models are powerful tools for evaluating pathogenesis, immune responses, vaccines, and therapeutics, including parasitic helminths. Helminths have also been tested as inflammatory disease therapeutics. This review focuses on immune responses during controlled infections with Trichuris species, Necator americanus, and Schistosoma mansoni. Over 700 participants have been experimentally infected across 33 studies to date. These models reveal significant heterogeneity in type 2-associated responses among individuals for all infections. While eosinophilia is most frequently observed, mixed Th1/Th2 responses in CD4+ T cells accompanied by IL-10 production and T regulatory cells are often observed in some individuals. Generally, controlled helminth infection models are safe and answer basic questions on type 2 responses. Improved immunophenotyping will guide future therapeutic applications and vaccine development.