Viewpoints Immunosuppression: Cause for Failures of Vaccines against African Trypanosomiases

Antibodies to the variant surface glyco-protein (VSG) are required for the control of African trypanosomes infecting the blood, whereas infections of the skin by low numbers of trypanosomes are con-trolled by innate resistance and do not require antibodies for their control. Low numbers of trypanosomes infecting the skin, although being killed by innate resistance, do not induce protection, but enhance susceptibility to re-infections due to suppression of innate resistance by adaptive immune responses. We propose to pursue a vaccine strategy that overcomes the induction of immuno-suppression but induces a Th1 imprint for protective immunity. We suggest that intradermal immunization with an opti-mally low dose of antigens of the whole parasite is necessary but not sufficient. We suggest that the immunization has to be accompanied by a treatment that inhibits the arginase pathway of antigen-present-ing cells (APCs), but modestly enhances their inducible nitric oxide synthase (iNOS) pathway to induce Th1 memory cells specific for crucial common antigens, which enhance innate resistance