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  • Review Article
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Developing vaccines to combat hookworm infection and intestinal schistosomiasis

Nature Reviews Microbiology volume 8, pages 814–826 (2010)Cite this article

Subjects

Key Points

  • Hookworm infection and schistosomiasis are two of the most common neglected tropical diseases of humans and among the most important in terms of their global disease burden in developing countries.

  • Global control of each infection currently relies on mass drug administration using donated or low-cost anthelmintic drugs, but high rates of both drug failure (with mebendazole) and post-treatment reinfection necessitate the development of anthelmintic vaccines.

  • A human hookworm vaccine is being developed as a bivalent injectable product combining two recombinant proteins, derived from the gut of the adult stage of the hookworm Necator americanus, that interfere with parasite blood feeding.

  • One of the leading schistosomiasis vaccines under development targets a tetraspanin antigen involved in biogenesis of the tegument of Schistosoma mansoni, the main etiological agent of intestinal schistosomiasis.

  • Both vaccines are being developed for children living in endemic areas of developing countries and could be linked to anthelmintic treatments in a programme of vaccine-linked chemotherapy.

  • Both the hookworm and schistosome antigens may ultimately be combined as a multivalent anthelmintic vaccine.

Abstract

Hookworm infection and schistosomiasis rank among the most important health problems in developing countries. Both cause anaemia and malnutrition, and schistosomiasis also results in substantial intestinal, liver and genitourinary pathology. In sub-Saharan Africa and Brazil, co-infections with the hookworm, Necator americanus, and the intestinal schistosome, Schistosoma mansoni, are common. The development of vaccines for these infections could substantially reduce the global disability associated with these helminthiases. New genomic, proteomic, immunological and X-ray crystallographic data have led to the discovery of several promising candidate vaccine antigens. Here, we describe recent progress in this field and the rationale for vaccine development.

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Figure 1: Global distributions and life cycles of hookworms and schistosomes.
Figure 2: Necator americanus degradation of host blood components and potential vaccine targets.
Figure 3: Schistosoma mansoni tegument.

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Acknowledgements

The authors acknowledge the support of the Bill & Melinda Gates Foundation, the National Health and Medical Research Council of Australia, and support from M. Hyman, C. Hyman, R. Zuckerberg and the Blavatnik Charitable Trust.

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Authors and Affiliations

  1. Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, 20037, Washington DC

    Peter J. Hotez, Jeffrey M. Bethony & David J. Diemert

  2. Sabin Vaccine Institute, 20037, Washington DC, USA

    Peter J. Hotez, Jeffrey M. Bethony & David J. Diemert

  3. Instituto René Rachou, Oswaldo Cruz Foundation, Belo Horizonte, 30190-002, Brazil

    Jeffrey M. Bethony & David J. Diemert

  4. Queensland Tropical Health Alliance, James Cook University, Cairns, QLD 4878, Australia

    Mark Pearson & Alex Loukas

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Glossary

Cercaria

The free-swimming larval stage of a trematode helminth such as Schistosoma mansoni.

Fibrosis

The formation of fibrous connective tissue that replaces normal organ tissue, usually in response to an insult such as injury or infection.

Ascariasis

A clinical syndrome associated with infection by the intestinal, soil-transmitted nematode helminth Ascaris lumbricoides.

Trichuriasis

A clinical syndrome associated with infection by the intestinal, soil-transmitted nematode helminth Trichuris trichiura.

Benzimidazole

A member of a class of anthelmintic medications (including albendazole and mebendazole) that are active against nematode worms.

Adjuvant

A substance that enhances, accelerates or prolongs antigen-specific immune responses when used in combination with specific vaccine antigens.

Urticaria

A skin rash that is characterized by raised erythematous, pruritic lesions and is most often associated with intradermal mast cell degranulation due to an immediate-type hypersensitivity reaction (known colloquially as 'hives').

Praziquantel

An anthelmintic medication that is active against flatworms, including trematodes (flukes) and tapeworms (cestodes).

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Hotez, P., Bethony, J., Diemert, D. et al. Developing vaccines to combat hookworm infection and intestinal schistosomiasis. Nat Rev Microbiol 8, 814–826 (2010). https://doi.org/10.1038/nrmicro2438

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