Vaccination against helminth parasites ‐ the ultimate challenge for vaccinologists?

Abstract

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.

The Serpin Secreted byBrugia malayiMicrofilariae, Bm-SPN-2, Elicits Strong, but Short-Lived, Immune Responses in Mice and Humans

“…There are few effective vaccines against helminth pathogens (25), and while chemotherapy is often curative, it provides no protection from reinfection. One of the remarkable features of the Mf stage of B. malayi is its longevity, which is likely to be many months in the bloodstream.…”

Down-Regulated Lymphoproliferation Coincides with Parasite Maturation and with the Collapse of Both Gamma Interferon and Interleukin-4 Responses in a Bovine Model of Onchocerciasis

“…Several mechanisms have been put forward to explain the underlying mechanisms of T-cell down-regulation in filariasis (20). In studies of lymphatic filariasis, IL-10 has been shown to regulate T-cell responses in both animal models and clinical studies (23,25).…”

Both Free-Living and Parasitic Nematodes Induce a Characteristic Th2 Response That Is Dependent on the Presence of Intact Glycans

“…A predominant feature of parasitic nematodes is their uniform ability to induce type 2 immune responses in their hosts, a feature that they share with other parasitic helminths (14,33). However, despite the extensive characterization of the immune responses to helminth infections, the antigens and mechanisms responsible for driving the distinct Th2 subset bias are still unknown.…”