Vaccination against helminth parasites--the ultimate challenge for vaccinologists?

Helminths are multicellular pathogens which infect vast numbers of human and animal hosts, causing widespread chronic disease and morbidity. Vaccination against these parasites requires more than identification of effective target antigens, because without understanding the immunology of the host-parasite relationship, ineffective immune mechanisms may be invoked, and there is a danger of amplifying immunopathogenic responses. The fundamental features of the immune response to helminths are therefore summarised in the context of vaccines to helminth parasites. The contention between type-1 and type-2 responses is a central issue in helminth infections, which bias the immune system strongly to the type-2 pathway. Evidence from both human and experimental animal infections indicates that both lineages contribute to immunity in differing circumstances, and that a balanced response leads to the most favourable outcome. A diversity of immune mechanisms can be brought to bear on various helminth species, ranging from antibody-independent macrophages, antibody-dependent granulocyte killing, and nonlymphoid actions, particularly in the gut. This diversity is highlighted by analysis of rodent infections, particularly in comparisons of cytokine-depleted and gene-targeted animals. This knowledge of protective mechanisms needs to be combined with a careful choice of parasite antigens for vaccines. Many existing candidates have been selected with host antibodies, rather than T-cell responses, and include a preponderance of highly conserved proteins with similarities to mammalian or invertebrate antigens. Advantage has yet to be taken of parasite genome projects, or of directed searches for novel, parasite-specific antigens and targets expressed only by infective stages and not mature forms which may generate immunopathology. With advances under way in parasite genomics and new vaccine delivery systems offering more rapid assessment and development, there are now excellent opportunities for new antihelminth vaccines.