Vaccination against helminth parasites - the ultimate challenge for vaccinologists?

Helminths are multicellular pathogens which infect vast numbers of human an d animal hosts, causing widspread chronic disease and morbidity. Vaccinatio n against these parasites requires more than identification of effective ta rget antigens, because without understanding the immunology of the host-par asite relationship, ineffective immune mechanisms may be invoked, and there is a danger of amplifying immunopathogenic responses. The fundamental feat ures of the immune response to helminths are therefore summarised in the co ntext 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 i mmunity in differing circumstances, and that a balanced response leads to t he most favourable outcome. A diversity of immune mechanisms can be brought to bear on various helminth species, ranging from antibody-independent mac rophages, antibody-dependent granulocyte killing, and non-lymphoid actions, particularly in the gut. This diversity is highlighted by analysis of rode nt infections, particularly in comparisons of cytokine-depleted and gene-ta rgeted animals. This knowledge of protective mechanisms needs to be combine d with a careful choice of parasite antigens for vaccines. Many existing ca ndidates have been selected with host antibodies, rather than T-cell respon ses, and include a preponderance of highly conserved proteins with similari ties to mammalian or invertebrate antigens. Advantage has yet to be taken o f parasite genome projects, or of directed searches for novel, parasite-spe cific antigens and targets expressed only by infective stages and not matur e forms which may generate immunopathology. With advances under way in para site genomics and new vaccine delivery systems offering more rapid assessme nt and development, there are now excellent opportunities for new antihelmi nth vaccines.