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Prospects for vaccination against pathogenic African trypanosomes

African trypanosomes cause human and animal African trypanosomiases, which are chronic, debilitating and often fatal diseases of people and livestock in sub‐Saharan Africa. The extracellular protozoan parasites are exemplars of antigenic variation. They direct host‐protective B‐cell and T‐cell immune responses towards hypervariable components of their variable surface glycoprotein coat and evade immune elimination by generating new surface coat antigenic variants at a rate that supersedes immune destruction. This results in recurring waves of parasitemia, tissue invasion and escalating immunopathology in trypanosomiasis‐susceptible hosts. Here, we discuss the possibility that host control of African trypanosomes might be improved by immunization with conserved VSG peptides and invariant surface glycoproteins. Infection‐induced T‐cell recall responses to these typically poorly expressed or nonimmunogenic parasite components induce tissue phagocytes to produce microbicidal materials that kill trypanosomes. Preliminary data that support this immune‐enhancing vaccine strategy are discussed, as are host and parasite interactions that might downregulate the protective responses. These include infection‐induced immunosuppression and increasing virulence of infecting parasites over time.