Hostname: page-component-76fb5796d-vfjqv Total loading time: 0 Render date: 2024-04-25T14:41:11.730Z Has data issue: false hasContentIssue false
  • English
  • Français

Vaccines against blood-feeding nematodes of humans and livestock

Published online by Cambridge University Press:  02 February 2007

J. M. BETHONY ,
A. LOUKAS ,
P. J. HOTEZ  and
D. P. KNOX
J. M. BETHONY
Affiliation:
Centro de Pesquisas René Rachou/CPqRR, A FIOCRUZ em Minas Gerais. Rene Rachou Research Center/CPqRR, The Oswaldo Cruz Foundation in the State of Minas Gerais, Brazil
A. LOUKAS
Affiliation:
Helminth Biology Laboratory, Division of Infectious Diseases and Immunology Queensland Institute of Medical Research, 300 Herston Rd, Herston, QLD 4006 Australia
P. J. HOTEZ
Affiliation:
Centro de Pesquisas René Rachou/CPqRR, A FIOCRUZ em Minas Gerais. Rene Rachou Research Center/CPqRR, The Oswaldo Cruz Foundation in the State of Minas Gerais, Brazil Dept. of Microbiology and Tropical Medicine, The George Washington University, Ross Hall, Room 736, 2300 Eye St. NW, Washington DC 20037
D. P. KNOX
Affiliation:
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, UK, EH26 0PZ
Get access Rights & Permissions [Opens in a new window]

Abstract

This paper summarises the progress towards vaccine development against the major blood-feeding nematodes of man and livestock, the hookworms and Haemonchus contortus, respectively. The impact of the diseases and the drivers for vaccine development are summarized as well as the anticipated impact of the host immune response on vaccine design. The performance requirements are discussed and progress towards these objectives using defined larval and adult antigens, many of these being shared between species. Specific examples include the Ancylostoma secreted proteins and homologues in Haemonchus as well as proteases used for digestion of the blood meal. This discussion shows that many of the major vaccine candidates are shared between these blood-feeding species, not only those from the blood-feeding stages but also those expressed by infective L3s in the early stages of infection. Challenges for the future include: exploiting the expanding genome information for antigen discovery, use of different recombinant protein expression systems, formulation with new adjuvants, and novel methods of field testing vaccine efficacy.

Keywords

HookwormsAncylostomaHaemonchusvaccineproteasesASPs
Type
Research Article
Information
Parasitology , Volume 133 , Supplement S2: Parasite Vaccines , October 2006 , pp. S63 - S79
Copyright
© 2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Aboobaker, A. A. and Blaxter, M. L. ( 2003). Use of RNA interference to investigate gene function in the human filarial nematode parasite Brugia malayi. Molecular and Biochemical Parasitology 129, 41–51.CrossRefGoogle Scholar
Albonico, M., Bickle, Q., Ramsan, M., Montresor, A., Savioli, L. and Taylor, M. ( 2003). Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar. Bulletin of the World Health Organization 81, 343–352.Google Scholar
Albonico, M., Smith, P. G., Ercole, E., Hall, A., Chwaya, H. M., Alawi, K. S. and Savioli, L. ( 1995). Rate of reinfection with intestinal nematodes after treatment of children with mebendazole or albendazole in a highly endemic area. Transactions of the Royal Society of Tropical Medicine and Hygiene 89, 538–541.CrossRefGoogle Scholar
Andrews, S. J., Rolph, T. P. and Munn, E. A. ( 1997). Duration of protective immunity against ovine haemonchosis following vaccination with the nematode gut membrane antigen H11. Research in Veterinary Science 62, 223–227.CrossRefGoogle Scholar
Ashman, K., Mather, J., Wiltshire, C., Jacobs, H. J. and Meeusen, E. ( 1995). Isolation of a larval surface glycoprotein from Haemonchus contortus and its possible role in evading host immunity. Molecular and Biochemical Parasitology 70, 175–179.CrossRefGoogle Scholar
Allen, J. E. and MacDonald, A. S. ( 1998). Profound suppression of cellular proliferation mediated by the secretions of nematodes. Parasite Immunology 20, 241–247.CrossRefGoogle Scholar
Asojo, O. A., Goud, G., Dhar, K., Loukas, A., Zhan, B., Deumic, V., Liu, S., Borgstahl, G. and Hotez, P. ( 2005). Novel X-ray structure of Na-ASP-2, a PR-1 protein from the nematode parasite Necator americanus and a vaccine antigen for human hookworm infection. Journal of Molecular Biology 346, 801–814.CrossRefGoogle Scholar
Bakker, N., Vervelde, L., Kanobana, K., Knox, D. P., Cornelissen, A. W., de Vries, E. and Yatsuda, A. P. ( 2004). Vaccination against the nematode Haemonchus contortus with a thiol-binding fraction from the excretory/secretory products (ES). Vaccine 22, 618–628.CrossRefGoogle Scholar
Balic, A., Bowles, V. M. and Meeusen, E. N. ( 2002). Mechanisms of immunity to Haemonchus contortus infection in sheep. Parasite Immunology 24, 39–46.CrossRefGoogle Scholar
Barnes, E. H. and Dobson, R. J. ( 1990). Population dynamics of Trichostrongylus colubriformis in sheep: computer model to simulate grazing systems and the evolution of anthelmintic resistance. International Journal for Parasitology 20, 823–831.CrossRefGoogle Scholar
Barnes, E. H., Dobson, R. J. and Barger, I. A. ( 1995). Worm control and anthelmintic resistance: adventures with a model. Parasitology Today 11, 56–63.CrossRefGoogle Scholar
Bennett, A. and Guyatt, H. ( 2000). Reducing intestinal nematode infections: efficacy of albendazole and mebendazole. Parasitology Today 16, 71–74.CrossRefGoogle Scholar
Bethony, J., Chen, J., Lin, S., Xiao, S., Zhan, Bi., Li, S., Xue, H., Xing, F., Humphries, D., Wang, Y., Chen, G., Foster, V., Hawdon, J. M. and Hotez, P. J. ( 2002). Emerging patterns of hookworm infection: influence of aging on the intensity of Necator infection in Hainan Province, Peoples Republic of China. Clinical Infectious Diseases 35, 1336–1344.CrossRefGoogle Scholar
Bethony, J. M., Loukas, A., Smout, M. J., Mendez, S., Wang, Y., Bottazzi, M. E., Zhan, B., Williamson, A. L., Lustigman, S., Correa-Oliveira, R., Xiao, S. H. and Hotez, P. J. ( 2005). Antibodies against a secreted protein from hookworm larvae reduce the intensity of infection in humans and vaccinated laboratory animals. FASEB Journal 19, 1743–1755.CrossRefGoogle Scholar
Bleakley, H. ( 2003). Disease and development: evidence from the American South. Journal of the European Economics Association 1, 376–386.CrossRefGoogle Scholar
Bowles, V. M., Brandon, M. R. and Meeusen, E. ( 1995). Characterization of local antibody responses to the gastrointestinal parasite Haemonchus contortus. Immunology 84, 669–674.Google Scholar
Brooker, S., Bethony, J. M., Rodrigues, L., Alexander, N., Geiger, S. and Hotez, P. J. ( 2005). Epidemiological, immunological and practical considerations in developing and evaluating a human hookworm vaccine. Expert Review of Vaccines 4, 35–50.CrossRefGoogle Scholar
Bundy, D. A., Chan, M. S. and Savioli, L. ( 1995). Hookworm infection in pregnancy. Transactions of the Royal Society of Tropical Medicine and Hygiene 89, 521–522.CrossRefGoogle Scholar
Bungiro, R. and Cappello, M. ( 2004). Hookworm infection: new developments and prospects for control. Current Opinions in Infectious Disease 17, 421–426.CrossRefGoogle Scholar
Cappello, M., Vlasuk, G. P., Bergum, P. W., Huang, S. and Hotez, P. J. ( 1995). Ancylostoma caninum anticoagulant peptide: a hookworm-derived inhibitor of human coagulation factor Xa. Proceedings of the National Academy of Sciences, USA 92, 6152–6156.CrossRefGoogle Scholar
Carr, A. and Pritchard, D. I. ( 1987). Antigen expression during development of the human hookworm, Necator americanus (Nematoda). Parasite Immunology 9, 219–234.CrossRefGoogle Scholar
Chadderdon, R. C. and Cappello, M. ( 1999). The hookworm platelet inhibitor: functional blockade of integrins GPIIb/IIIa (alphaIIbbeta3) and GPIa/IIa (alpha2beta1) inhibits platelet aggregation and adhesion in vitro. Journal of Infectious Diseases 179, 235–241.CrossRefGoogle Scholar
Chan, M. S. ( 1997). The global burden of intestinal nematode infections – fifty years on. Parasitology Today 13, 438–443.CrossRefGoogle Scholar
Chan, M. S., Bradley, M. and Bundy, D. A. P. ( 1997). Transmission patterns and the epidemiology of hookworm. International Journal for Parasitology 26, 1392–1400.Google Scholar
Chow, S. C., Brown, A. and Pritchard, D. ( 2000). The human hookworm pathogen Necator americanus induces apoptosis in T lymphocytes. Parasite Immunology 22, 21–29.CrossRefGoogle Scholar
Christian, P., Khatry, S. K. and West, J. P. Jr. ( 2004). Antenatal anthelminthic treatment, birthweight, and infant survival in rural Nepal. Lancet 364, 981–983.CrossRefGoogle Scholar
Culley, F. J., Brown, A., Conroy, D. M., Sabroe, I., Pritchard, D. I. and Williams, T. J. ( 2000). Eotaxin is specifically cleaved by hookworm metalloproteases preventing its action in vitro and in vivo. Journal of Immunology 165, 6447–6453.CrossRefGoogle Scholar
Del Valle, A., Jones, B. F., Harrison, L. M., Chadderdon, R. C. and Cappello, M. ( 2003). Isolation and molecular cloning of a secreted hookworm platelet inhibitor from adult Ancylostoma caninum. Molecular and Biochemical Parasitology 129, 167–177.CrossRefGoogle Scholar
DeSilva, N., Brooker, S., Hotez, P., Montresor, A., Engels, D. and Savioli, L. ( 2003). Soil-transmitted helminth infections: updating the global picture. Trends in Parasitology 12, 547–551.CrossRefGoogle Scholar
Emery, D. L., McClure, S. J. and Wagland, B. M. ( 1993). Production of vaccines against gastrointestinal nematodes of livestock. Immunology and Cell Biology 71, 463–472.CrossRefGoogle Scholar
Emery, D. L. and Wagland, B. M. ( 1991). Vaccines against gastrointestinal nematode parasites of ruminants. Parasitology Today 7, 347–349.CrossRefGoogle Scholar
Fujiwara, R. T., Loukas, A., Mendez, S., Williamson, A. L., Bueno, L. L., Wang, Y., Samuel, A., Hotez, P. J. and Bethony, J. M. ( 2006). Vaccination with irradiated Ancylostoma caninum third stage larvae induces a Th2-like response in dogs. Vaccine 24, 501–509.CrossRefGoogle Scholar
Geiger, S. M., Massara, C. L., Bethony, J., Soboslay, P. T. and Correa-Oliveira, R. ( 2004). Cellular responses and cytokine production in post-treatment hookworm patients from an endemic area in Brazil. Clinical Experimental Immunology 136, 334–340.CrossRefGoogle Scholar
Geldhof, P., Murray, L., Couthier, A., Gilleard, J. S., McLauchlan, G., Knox, D. P. and Britton, C. ( 2006). Testing the efficacy of RNA interference in Haemonchus contortus. International Journal for Parasitology 36, 801–810.CrossRefGoogle Scholar
Geldhof, P., Newlands, G. F., Nyame, K., Cummings, R., Smith, W. D. and Knox, D. P. ( 2005). Presence of the LDNF glycan on the host-protective H-gal-GP fraction from Haemonchus contortus. Parasite Immunology 27, 55–60.CrossRefGoogle Scholar
Ghosh, K., Hawdon, J. and Hotez, P. ( 1996). Vaccination with alum-precipitated recombinant Ancylostoma-secreted protein 1 protects mice against challenge infections with infective hookworm (Ancylostoma caninum) larvae. Journal of Infectious Diseases 174, 1380–1383.CrossRefGoogle Scholar
Ghosh, K. and Hotez, P. J. ( 1999). Antibody-dependent reductions in mouse hookworm burden after vaccination with Ancylostoma caninum secreted protein 1. Journal of Infectious Diseases 180, 1674–1681.CrossRefGoogle Scholar
Gill, H. S., Husband, A. J. and Watson, D. L. ( 1992). Localization of immunoglobulin-containing cells in the abomasum of sheep following infection with Haemonchus contortus. Veterinary Immunology and Immunopathology 31, 179–187.CrossRefGoogle Scholar
Girod, N., Brown, A., Pritchard, D. I. and Billett, E. E. ( 2003). Successful vaccination of BALB/c mice against human hookworm (Necator americanus): the immunological phenotype of the protective response. International Journal for Parasitology 33, 71–80.CrossRefGoogle Scholar
Goldberg, D. E. ( 2005). Haemoglobin degradation. Current Topics in Microbiology and Immunology 295, 275–291.Google Scholar
Goud, G. N., Bottazzi, M. E., Zhan, B., Mendez, S., Deumic, V., Plieskatt, J., Liu, S., Wang, Y., Bueno, L., Fujiwara, R., Samuel, A., Ahn, S. Y., Solanki, M., Asojo, O. A., Wang, J., Bethony, J. M., Loukas, A., Roy, M. and Hotez, P. J. ( 2005). Expression of the Necator americanus hookworm larval antigen Na-ASP-2 in Pichia pastoris and purification of the recombinant protein for use in human clinical trials. Vaccine 23, 4754–4764.CrossRefGoogle Scholar
Goud, G. N., Zhan, B., Ghosh, K., Loukas, A., Hawdon, J., Dobardzic, A., Deumic, V., Liu, S., Dobardzic, R., Zook, R. C., Qun, J., Liu, Y. Y., Hoffman, L., Chung-Debose, D., Patel, R., Mendez, S. and Hotez, P. J. ( 2004). Cloning, yeast expression, isolation and vaccine testing of recombinant Ancylostoma secreted protein 1 (ASP-1) and ASP-2 from Ancylostoma ceylanicum. Journal of Infectious Diseases 189, 919–929.CrossRefGoogle Scholar
Haslam, S. M., Coles, G. C., Munn, E. A., Smith, T. S., Smith, H. F., Morris, H. R. and Dell, A. ( 1996). Haemonchus contortus glycoproteins contain oligosaccharides with novel highly fucosylated core structures. Journal of Biological Chemistry 271, 30561–30570.CrossRefGoogle Scholar
Hawdon, J. M. and Hotez, P. J. ( 1996). Hookworm: developmental biology of the infectious process. Current Opinions on Genetic Development 6, 618–623.CrossRefGoogle Scholar
Hawdon, J. M., Jones, B. F., Hoffman, D. R. and Hotez, P. J. ( 1996). Cloning and characterization of Ancylostoma-secreted protein. A novel protein associated with the transition to parasitism by infective hookworm larvae. Journal of Biological Chemistry 271, 6672–6678.Google Scholar
Hawdon, J. M., Narasimhan, S. and Hotez, P. J. ( 1999). Ancylostoma secreted protein 2: cloning and characterization of a second member of a family of nematode secreted proteins from Ancylostoma caninum. Molecular and Biochemical Parasitology 99, 149–165.CrossRefGoogle Scholar
Hein, W. R. and Mackay, C. R. ( 1991). Prominence of gamma delta T cells in the ruminant immune system. Immunology Today 12, 30–34.CrossRefGoogle Scholar
Horton, J. ( 2003). Global anthelmintic chemotherapy programs: learning from history. Trends in Parasitology 19, 405–409.CrossRefGoogle Scholar
Hotez, P. J., Bethony, J., Bottazzi, M. E., Brooker, S. and Buss, P. ( 2005). Hookworm – “the great infection of mankind.” PLoS Medicine 2, e67 177–181.CrossRefGoogle Scholar
Hotez, P., Brooker, S., Bethony, J., Bottazzi, M., Loukas, A. and Xiao, S. ( 2004 a). Current Concepts: Hookworm Infection. New England Journal of Medicine 351, 799–807.Google Scholar
Hotez, P. J., Zhan, B., Bethony, J. M., Loukas, A., Williamson, A., Goud, G. N., Hawdon, J. M., Dobardzic, A., Dobardzic, R., Ghosh, K., Bottazzi, M. E., Mendez, S., Zook, B., Wang, Y., Liu, S., Essiet-Gibson, I., Chung-Debose, S., Xiao, S. H., Knox, D., Megher, M., Inan, M., Correa-Oliveira, R., Vilk, P., Shepherd, H. R., Brandt, W. and Russell, P. K. ( 2003). Progress in the development of a recombinant vaccine for human hookworm disease: the human hookworm vaccine initiative. International Journal for Parasitology 33, 1245–1258.CrossRefGoogle Scholar
Hsieh, G. C., Loukas, A., Wahl, A. M., Bhatia, M., Wang, Y., Williamson, A. L., Kehn, K. W., Maruyama, H., Hotez, P. J., Leitenberg, D., Bethony, J. and Constant, S. L. ( 2004). A secreted protein from the human hookworm Necator americanus binds selectively to NK cells and induces IFN-gamma production. Journal of Immunology 173, 2699–2704.CrossRefGoogle Scholar
Hussein, A. S., Kichenin, K. and Selkirk, M. E. ( 2002). Suppression of secreted acetylcholinesterase expression in Nippostrongylus brasiliensis by RNA interference. Molecular and Biochemical Parasitology 122, 91–94.CrossRefGoogle Scholar
Issa, Z., Grant, W. N., Stasiuk, S. and Shoemaker, C. B. ( 2005). Development of methods for RNA interference in the sheep gastrointestinal parasite, Trichostrongylus colubriformis. International Journal for Parasitology 35, 935–940.CrossRefGoogle Scholar
Jacobs, H. J., Wiltshire, C., Ashman, K. and Meeusen, E. N. ( 1999). Vaccination against the gastrointestinal nematode, Haemonchus contortus, using a purified larval surface antigen. Vaccine 17, 362–368.CrossRefGoogle Scholar
Jarrett, E. and Bazin, H. ( 1974). Elevation of total serum IgE in rats following helminth parasite infection. Nature 251, 613–614.CrossRefGoogle Scholar
Jasmer, D. P., Perryman, L. E., Conder, G. A., Crow, S. and McGuire, T. ( 1993). Protective immunity to Haemonchus contortus induced by immunoaffinity isolated antigens that share a phylogenetically conserved carbohydrate gut surface epitope. Journal of Immunology 151, 5450–5460.Google Scholar
Jasmer, D. P., Perryman, L. E. and McGuire, T. C. ( 1996). Haemonchus contortus GA1 antigens: related, phospholipase C-sensitive, apical gut membrane proteins encoded as a polyprotein and released from the nematode during infection. Proceedings of the National Academy of Sciences, USA 93, 8642–8647.CrossRefGoogle Scholar
Kabagambe, E. K., Barras, S. R., Li, Y., Pena, M. T., Smith, W. D. and Miller, J. E. ( 2000). Attempts to control haemonchosis in grazing ewes by vaccination with gut membrane proteins of the parasite. Veterinary Parasitology 92, 15–23.CrossRefGoogle Scholar
Kaplan, R. M. ( 2004). Drug resistance in nematodes of veterinary importance: a status report. Trends in Parasitology 20, 477–481.CrossRefGoogle Scholar
Klei, T. R. ( 1997). Immunological control of gastrointestinal nematode infections. Veterinary Parasitology 72, 507–516.CrossRefGoogle Scholar
Knox, D. P. ( 2000). Development of vaccines against gastrointestinal nematodes. Parasitology 120 (Suppl.), S43–61.CrossRefGoogle Scholar
Knox, D. P., Redmond, D. L., Newlands, G. F., Skuce, P. J., Pettit, D. and Smith, W. D. ( 2003). The nature and prospects for gut membrane proteins as vaccine candidates for Haemonchus contortus and other ruminant trichostrongyloids. International Journal for Parasitology 33, 1129–1137.CrossRefGoogle Scholar
Knox, D. P. and Smith, W. D. ( 2001). Vaccination against gastrointestinal nematode parasites of ruminants using gut-expressed antigens. Veterinary Parasitology 100, 21–32.CrossRefGoogle Scholar
Knox, D. P., Smith, S. K. and Smith, W. D. ( 1999). Immunization with an affinity purified protein extract from the adult parasite protects lambs against infection with Haemonchus contortus. Parasite Immunology 21, 201–210.CrossRefGoogle Scholar
Kooyman, F. N., Schallig, H. D., Van Leeuwen, M. A., MacKellar, A., Huntley, J. F., Cornelissen, A. W. and Vervelde, L. ( 2000). Protection in lambs vaccinated with Haemonchus contortus antigens is age related, and correlates with IgE rather than IgG1 antibody. Parasite Immunology 22, 13–20.CrossRefGoogle Scholar
Loeb, L. and Smith, A. J. ( 1904). The presence of a substance inhibiting the coagulation of blood in the anchylostoma. Proceedings of the Pathological Society of Philadelphia 7, 173–178.Google Scholar
Longbottom, D., Redmond, D. L., Russell, M., Liddell, S., Smith, W. D. and Knox, D. P. ( 1997). Molecular cloning and characterisation of a putative aspartate proteinase associated with a gut membrane protein complex from adult Haemonchus contortus. Molecular and Biochemical Parasitology 88, 63–72.CrossRefGoogle Scholar
Loukas, A., Bethony, J. M., Mendez, S., Fujiwara, R. T., Goud, G. N., Ranjit, N., Zhan, B., Jones, K., Bottazzi, M. E. and Hotez, P. J. ( 2005 b). Vaccination with recombinant aspartic hemoglobinase reduces parasite load and blood loss after hookworm infection in dogs. PLoS Medicine 2, e295.Google Scholar
Loukas, A., Bethony, J. M., Williamson, A. L., Goud, G. N., Mendez, S., Zhan, B., Hawdon, J. M., Bottazzi, M. E., Brindley, P. J. and Hotez, P. J. ( 2004). Vaccination of dogs with a recombinant cysteine protease from the intestine of canine hookworms diminishes the fecundity and growth of worms. Journal of Infectious Diseases 189, 1952–1961.CrossRefGoogle Scholar
Loukas, A., Constant, S. L. and Bethony, J. M. ( 2005 a). Immunobiology of hookworm infection. FEMS Immunology and Medical Microbiology 43, 115–124.Google Scholar
Loukas, A. and Prociv, P. ( 2001). Immune responses in hookworm infections. Clinical Microbiology Reviews 14, 689–703.CrossRefGoogle Scholar
Lustigman, S., Zhang, J., Liu, J., Oksov, Y. and Hashmi, S. ( 2004). RNA interference targeting cathepsin L and Z-like cysteine proteases of Onchocerca volvulus confirmed their essential function during L3 molting. Molecular and Biochemical Parasitology 138, 165–170.CrossRefGoogle Scholar
Maizels, R. M., Holland, M. J., Falcone, F. H., Zang, X. X. and Yazdanbakhsh, M. ( 1999). Vaccination against helminth parasites – the ultimate challenge for vaccinologists? Immunological Reviews 171, 125–147.Google Scholar
Manton, V. J. A., Peacock, R., Poynter, D., Silverman, P. H. and Terry, R. J. ( 1962). The influence of age on naturally-acquired resistance to Haemonchus contortus in young lambs. Research in Veterinary Science 1, 308–314.Google Scholar
Meeusen, E. N. and Balic, A. ( 2000). Do eosinophils have a role in the killing of helminth parasites? Parasitology Today 16, 95–101.Google Scholar
Meeusen, E. N., Balic, A. and Bowles, V. ( 2005). Cells, cytokines and other molecules associated with rejection of gastrointestinal nematode parasites. Veterinary Immunology and Immunopathology 108, 121–125.CrossRefGoogle Scholar
Mendez, S., Zhan, B., Goud, G., Ghosh, K., Dobardzic, A., Wu, W. H., Liu, S., Deumic, V., Dobardzic, R., Liu, Y. Y., Bethony, J. and Hotez, P. J. ( 2005). Effect of combining the larval antigens Ancylostoma secreted protein 2 (ASP-2) and metalloprotease 1 (MTP-1) in protecting hamsters against hookworm infection and disease caused by Ancylostoma ceylanicum. Vaccine 23, 3123–3130.CrossRefGoogle Scholar
Mieszczanek, J., Harrison, L. M., Vlasuk, G. P. and Cappello, M. ( 2004). Anticoagulant peptides from Ancylostoma caninum are immunologically distinct and localize to separate structures within the adult hookworm. Molecular and Biochemical Parasitology 133, 319–323.CrossRefGoogle Scholar
Miguel, E. A. and Kremer, M. ( 2003). Worms: identifying impacts on education and health in the presence of treatment externalities. Econometrica 72, 159–217.Google Scholar
Miller, T. A. ( 1965 a). Effect of age of the dog on immunogenic efficiency of double vaccination with X-irradiated Ancylostoma caninum larvae. American Journal of Veterinary Research 26, 1383–1390.Google Scholar
Miller, T. A. ( 1965 b). Persistence of immunity following double vaccination of pups with X-irradiated Ancylostoma caninum larvae. Journal of Parasitology 51, 705–711.Google Scholar
Miller, T. A. ( 1978). Industrial development and field use of the canine hookworm vaccine. Advances in Parasitology 16, 333–342.CrossRefGoogle Scholar
Mitreva, M., McCarter, J. P., Arasu, P., Hawdon, J., Martin, J., Dante, M., Wylie, T., Xue, J., Stajich, J., Kapulkin, W., Clifton, S. W., Waterston, R. H. and Wilson, R. K. ( 2005). Investigating hookworm genomes by comparative analysis of two Ancylostoma species. BMC Genomics 6, 58.CrossRefGoogle Scholar
Molyneux, D. H., Hotez, P. J. and Fenwick, A. ( 2005). “Rapid impact” interventions: how a policy of integrated control for Africa's neglected tropical diseases could benefit the poor. PLoS Medicine 2, e336.CrossRefGoogle Scholar
Munn, E. A., Smith, T. S., Smith, H., James, F. M., Smith, F. C. and Andrews, S. J. ( 1997). Vaccination against Haemonchus contortus with denatured forms of the protective antigen H11. Parasite Immunology 19, 243–248.CrossRefGoogle Scholar
Newlands, G. F., Skuce, P. J., Knox, D. P. and Smith, W. D. ( 2000). Cloning and expression of cystatin, a potent cysteine protease inhibitor from the gut of Haemonchus contortus. Parasitology 122, 371–378.Google Scholar
Newlands, G. F., Skuce, P. J., Knox, D. P., Smith, S. K. and Smith, W. D. ( 1999). Cloning and characterization of a beta-galactoside-binding protein (galectin) from the gut of the gastrointestinal nematode parasite Haemonchus contortus. Parasitology 119, 483–490.CrossRefGoogle Scholar
Newton, S. E. and Munn, E. A. ( 1999). The development of vaccines against gastrointestinal nematode parasites, particularly Haemonchus contortus. Parasitology Today 15, 116–122.CrossRefGoogle Scholar
Nokes, C., Grantham-McGregor, S. M., Sawyer, A. W., Cooper, E. S., Robinson, B. A. and Bundy, D. A. ( 1992). Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children. Parasitology 104, 539–547.CrossRefGoogle Scholar
Pritchard, D. I. and Brown, A. ( 2001). Is Necator americanus approaching a mutualistic symbiotic relationship with humans? Trends in Parasitology 17, 169–172.Google Scholar
Pritchard, D. I., Quinnell, R. J. and Walsh, E. A. ( 1995). Immunity in humans to Necator americanus: IgE, parasite weight and fecundity. Parasite Immunology 17, 71–75.CrossRefGoogle Scholar
Pritchard, D. I., Walsh, E. A., Quinell, R. J., Raiko, A., Edmonds, P. and Keymer, A. E. ( 1992). Isotypic variation in antibody responses in a community in Papua New Guinea to larval and adult antigens during infection, and following reinfection, with the hookworm Necator americanus. Parasite Immunology 14, 617–631.CrossRefGoogle Scholar
Quinnell, R. J., Pritchard, D. I., Raiko, A., Brown, A. P. and Shaw, M. A. ( 2004). Immune responses in human necatoriasis: association between interleukin-5 responses and resistance to reinfection. Journal of Infectious Diseases 190, 430–438.CrossRefGoogle Scholar
Rainbird, M. A., Macmillan, D. and Meeusen, E. N. ( 1998). Eosinophil-mediated killing of Haemonchus contortus larvae: effect of eosinophil activation and role of antibody, complement and interleukin-5. Parasite Immunology 20, 93–103.CrossRefGoogle Scholar
Ranjit, N., Jones, M. K., Stenzel, D. J., Gasser, R. B. and Loukas, A. ( 2006). A survey of the intestinal transcriptomes of the hookworms, Necator americanus and Ancylostoma caninum, using tissues isolated by laser microdissection microscopy. International Journal for Parasitology, In press.CrossRefGoogle Scholar
Redmond, D. L. and Knox, D. P. ( 2004). Protection studies in sheep using affinity-purified and recombinant cysteine proteinases of adult Haemonchus contortus. Vaccine 22, 4252–4261.CrossRefGoogle Scholar
Redmond, D. L. and Knox, D. P. ( 2006). Further protection studies using recombinant forms of Haemonchus contortus cysteine proteinases. Parasite Immunology, In press.CrossRefGoogle Scholar
Redmond, D. L., Knox, D. P., Newlands, G. and Smith, W. D. ( 1997). Molecular cloning and characterisation of a developmentally regulated putative metallopeptidase present in a host protective extract of Haemonchus contortus. Molecular and Biochemical Parasitology 85, 77–87.CrossRefGoogle Scholar
Roche, M. and Layrisse, M. ( 1966). The nature and causes of “hookworm anemia”. American journal of Tropical Medicine and Hygiene 15, 1029–1102.CrossRefGoogle Scholar
Schallig, H. D. ( 2000). Immunological responses of sheep to Haemonchus contortus. Parasitology 120 (Suppl), S63–72.CrossRefGoogle Scholar
Schallig, H. D. and van Leeuwen, M. A. ( 1997). Protective immunity to the blood-feeding nematode Haemonchus contortus induced by vaccination with parasite low molecular weight antigens. Parasitology 114, 293–299.CrossRefGoogle Scholar
Schallig, H. D., van Leeuwen, M. A. and Hendrikx, W. M. ( 1994). Immune responses of Texel sheep to excretory/secretory products of adult Haemonchus contortus. Parasitology 108, 351–357.CrossRefGoogle Scholar
Sharp, P. J. and Wagland, B. M. ( 1996). Haemonchus contortus vaccine. US Patent 5525508, 1996.
Skuce, P. J., Newlands, G. F., Stewart, E. M., Pettit, D., Smith, S. K., Smith, W. D. and Knox, D. P. ( 2001). Cloning and characterisation of thrombospondin, a novel multidomain glycoprotein found in association with a host protective gut extract from Haemonchus contortus. Molecular and Biochemical Parasitology 117, 241–244.CrossRefGoogle Scholar
Smith, T. S., Graham, M., Munn, E. A., Newton, S. E., Knox, D. P., Coadwell, W. J., McMichael-Phillips, D., Smith, H., Smith, W. D. and Oliver, J. J. ( 1997). Cloning and characterization of a microsomal aminopeptidase from the intestine of the nematode Haemonchus contortus. Biochimica et Biophysics Acta 1338, 295–306.CrossRefGoogle Scholar
Smith, T. S., Munn, E. A., Graham, M., Tavernor, A. S. and Greenwood, C. A. ( 1993). Purification and evaluation of the integral membrane protein H11 as a protective antigen against Haemonchus contortus. International Journal for Parasitology 23, 271–280.CrossRefGoogle Scholar
Smith, W. D. and Angus, K. W. ( 1980). Haemonchus contortus: attempts to immunise lambs with irradiated larvae. Research in Veterinary Science 29, 45–50.Google Scholar
Smith, W. D., Newlands, G. F., Smith, S. K., Pettit, D. and Skuce, P. J. ( 2003). Metalloendopeptidases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep. Parasite Immunology 25, 313–323.CrossRefGoogle Scholar
Smith, W. D. and Smith, S. K. ( 1993). Evaluation of aspects of the protection afforded to sheep immunised with a gut membrane protein of Haemonchus contortus. Research in Veterinary Science 55, 1–9.CrossRefGoogle Scholar
Smith, W. D., Smith, S. K. and Murray, J. M. ( 1994). Protection studies with integral membrane fractions of Haemonchus contortus. Parasite Immunology 16, 231–241.CrossRefGoogle Scholar
Smith, W. D., van Wyk, J. A. and van Strijp, M. F. ( 2001). Preliminary observations on the potential of gut membrane proteins of Haemonchus contortus as candidate vaccine antigens in sheep on naturally infected pasture. Veterinary Parasitology 98, 285–297.CrossRefGoogle Scholar
Stanssens, P., Bergum, P. M., Gansemans, Y., Jespers, L., Laroche, Y., Huang, S., Maki, S., Messens, J., Lauwereys, M., Cappello, M., Hotez, P. J., Lasters, I. and Vlasuk, G. P. ( 1996). Anticoagulant repertoire of the hookworm Ancylostoma caninum. Proceedings of the National Academy of Sciences, USA 93, 2149–2154.CrossRefGoogle Scholar
Stephenson, L. S., Latham, M. C., Adams, E. J., Kinoti, S. N. and Pertet, A. ( 1993). Physical fitness, growth and appetite of Kenyan school boys with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved four months after a single dose of albendazole. Journal of Nutrition 123, 1036–1046.Google Scholar
Stephenson, L. S., Latham, M. C., Kinoti, S. N., Kurz, K. M. and Brigham, H. ( 1990). Improvements in physical fitness of Kenyan schoolboys infected with hookworm, Trichuris trichiura and Ascaris lumbricoides following a single dose of albendazole. Transactions of the Royal Society of Tropical Medicine and Hygiene 84, 277–282.CrossRefGoogle Scholar
Stephenson, L. S., Latham, M. C., Kurz, K. M., Kinoti, S. N. and Brigham, H. ( 1989). Treatment with a single dose of albendazole improves growth of Kenyan schoolchildren with hookworm, Trichuris trichiura, and Ascaris lumbricoides infections. American Journal of Tropical Medicine and Hygiene 41, 78–87.CrossRefGoogle Scholar
Stoltzfus, R. J., Albonico, M., Chwaya, H. M., Savioli, L., Tielsch, J., Schulze, K. and Yip, R. ( 1996). Hemoquant determination of hookworm-related blood loss and its role in iron deficiency in African children. American Journal of Tropical Medicine and Hygiene 55, 399–404.CrossRefGoogle Scholar
Stoltzfus, R. J., Albonico, M., Chwaya, H. M., Tielsch, J. M., Schulze, K. J. and Savioli, L. ( 1998). Effects of the Zanzibar school-based deworming program on iron status of children. American Journal of Clinical Nutrition 68, 179–186.CrossRefGoogle Scholar
Stoltzfus, R. J., Chwaya, H. M., Tielsch, J. M., Schulze, K. J., Albonico, M. and Savioli, L. ( 1997 a). Epidemiology of iron deficiency anemia in Zanzibari schoolchildren: the importance of hookworms. American Journal of Clinical Nutrition 65, 153–159.Google Scholar
Stoltzfus, R. J., Dreyfuss, M. L., Chwaya, H. M. and Albonico, M. ( 1997 b). Hookworm control as a strategy to prevent iron deficiency. Nutrition Reviews 55, 223–232.Google Scholar
Tatar, M. and Yin, C. ( 2001). Slow aging during insect reproductive diapause: why butterflies, grasshoppers and flies are like worms. Experimental Gerontology 36, 723–738.CrossRefGoogle Scholar
Todd, C. W. and Colley, D. G. ( 2002). Practical and ethical issues in the development of a vaccine against schistosomiasis mansoni. American Journal of Tropical Medicine and Hygiene 66, 348–358.CrossRefGoogle Scholar
Urquhart, G. M., Armour, J., Duncan, J. L., Dunn, A. M. and Jennings, F. W. ( 1987). Veterinary Parasitology. Longman Scientific and Technical, Essex, U.K.
Urquhart, G. M., Jarrett, W. F., Jennings, F. W., McIntyre, W. I., Mulligan, W. and Sharp, N. C. ( 1966). Immunity to Haemonchus contortus infection. Failure of γ-irradiated larvae to immunize young lambs. American Journal of Veterinary Research 27, 1641–1643.Google Scholar
Vervelde, L., Kooyman, F. N., Van Leeuwen, M. A., Schallig, H. D., MacKellar, A., Huntley, J. F. and Cornelissen, A. W. ( 2001). Age-related protective immunity after vaccination with Haemonchus contortus excretory/secretory proteins. Parasite Immunology 23, 419–426.CrossRefGoogle Scholar
Vervelde, L., Van Leeuwen, M. A., Kruidenier, M., Kooyman, F. N., Huntley, J. F., Van Die, I. and Cornelissen, A. W. ( 2002). Protection studies with recombinant excretory/secretory proteins of Haemonchus contortus. Parasite Immunology 24, 189–201.CrossRefGoogle Scholar
Watson, D. L. and Gill, H. S. ( 1991). Effect of weaning on antibody responses and nematode parasitism in Merino lambs. Research in Veterinary Science 51, 128–132.CrossRefGoogle Scholar
Willadsen, P. ( 2004). Anti-tick vaccines. Parasitology 129 (Suppl), S367–387.CrossRefGoogle Scholar
Williamson, A. L., Brindley, P. J., Abbenante, G., Prociv, P., Berry, C., Girdwood, K., Pritchard, D. I., Fairlie, D. P., Hotez, P. J., Dalton, J. P. and Loukas, A. ( 2002). Cleavage of hemoglobin by hookworm cathepsin D aspartic proteases and its potential contribution to host specificity. FASEB Journal 16, 1458–1460.CrossRefGoogle Scholar
Williamson, A. L., Brindley, P. J., Knox, D. P., Hotez, P. J. and Loukas, A. ( 2003). Digestive proteases of blood-feeding nematodes. Trends in Parasitology 19, 417–423.CrossRefGoogle Scholar
Williamson, A. L., Lecchi, P., Turk, B. E., Choe, Y., Hotez, P. J., McKerrow, J. H., Cantley, L. C., Sajid, M. and Loukas, A. ( 2004). A multi-enzyme cascade of hemoglobin proteolysis in the intestine of blood-feeding hookworms. Journal of Biological Chemistry 279, 3560–3567.CrossRefGoogle Scholar
Williamson, A. L., Lustigman, S., Oksov, Y., Deumic, V., Plieskatt, J., Mendez, S., Zhan, B., Bottazzi, M. E., Hotez, P. J. and Loukas, A. ( 2006). Ac-MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration. Infection and Immunity 74, 961–967.CrossRefGoogle Scholar
World Health Organization ( 2002). Prevention and control of schistosomiasis and soil-transmitted helminthiases. WHO Technical Report Series, number 912. Geneva: World Health Organization.
Yatsuda, A. P., Krijgsveld, J., Cornelissen, A. W., Heck, A. J. and de Vries, E. ( 2002). Comprehensive analysis of the secreted proteins of the parasite Haemonchus contortus reveals extensive sequence variation and differential immune recognition. Journal of Biological Chemistry 278, 16941–6951.Google Scholar
Zhan, B., Hotez, P. J., Wang, Y. and Hawdon, J. M. ( 2002). A developmentally regulated metalloprotease secreted by host-stimulated Ancylostoma caninum third-stage infective larvae is a member of the astacin family of proteases. Molecular and Biochemical Parasitology 120, 291–296.CrossRefGoogle Scholar
Zhan, B., Liu, S., Perally, S., Xue, J., Fujiwara, R., Brophy, P., Xiao, S., Liu, Y., Feng, J., Williamson, A., Wang, Y., Bueno, L. L., Mendez, S., Goud, G., Bethony, J. M., Hawdon, J. M., Loukas, A., Jones, K. and Hotez, P. J. ( 2005). Biochemical characterization and vaccine potential of a heme-binding glutathione transferase from the adult hookworm Ancylostoma caninum. Infection and Immunity 73, 6903–6911.CrossRefGoogle Scholar