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Vaccines against blood-feeding nematodes of humans and livestock

  • J. M. BETHONY (a1), A. LOUKAS (a2), P. J. HOTEZ (a1) (a3) and D. P. KNOX (a4)

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.

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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, 4151.
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, 343352.
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, 538541.
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, 223227.
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, 175179.
Allen, J. E. and MacDonald, A. S. ( 1998). Profound suppression of cellular proliferation mediated by the secretions of nematodes. Parasite Immunology 20, 241247.
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, 801814.
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, 618628.
Balic, A., Bowles, V. M. and Meeusen, E. N. ( 2002). Mechanisms of immunity to Haemonchus contortus infection in sheep. Parasite Immunology 24, 3946.
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, 823831.
Barnes, E. H., Dobson, R. J. and Barger, I. A. ( 1995). Worm control and anthelmintic resistance: adventures with a model. Parasitology Today 11, 5663.
Bennett, A. and Guyatt, H. ( 2000). Reducing intestinal nematode infections: efficacy of albendazole and mebendazole. Parasitology Today 16, 7174.
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, 13361344.
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, 17431755.
Bleakley, H. ( 2003). Disease and development: evidence from the American South. Journal of the European Economics Association 1, 376386.
Bowles, V. M., Brandon, M. R. and Meeusen, E. ( 1995). Characterization of local antibody responses to the gastrointestinal parasite Haemonchus contortus. Immunology 84, 669674.
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, 3550.
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, 521522.
Bungiro, R. and Cappello, M. ( 2004). Hookworm infection: new developments and prospects for control. Current Opinions in Infectious Disease 17, 421426.
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, 61526156.
Carr, A. and Pritchard, D. I. ( 1987). Antigen expression during development of the human hookworm, Necator americanus (Nematoda). Parasite Immunology 9, 219234.
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, 235241.
Chan, M. S. ( 1997). The global burden of intestinal nematode infections – fifty years on. Parasitology Today 13, 438443.
Chan, M. S., Bradley, M. and Bundy, D. A. P. ( 1997). Transmission patterns and the epidemiology of hookworm. International Journal for Parasitology 26, 13921400.
Chow, S. C., Brown, A. and Pritchard, D. ( 2000). The human hookworm pathogen Necator americanus induces apoptosis in T lymphocytes. Parasite Immunology 22, 2129.
Christian, P., Khatry, S. K. and West, J. P. Jr. ( 2004). Antenatal anthelminthic treatment, birthweight, and infant survival in rural Nepal. Lancet 364, 981983.
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, 64476453.
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, 167177.
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, 547551.
Emery, D. L., McClure, S. J. and Wagland, B. M. ( 1993). Production of vaccines against gastrointestinal nematodes of livestock. Immunology and Cell Biology 71, 463472.
Emery, D. L. and Wagland, B. M. ( 1991). Vaccines against gastrointestinal nematode parasites of ruminants. Parasitology Today 7, 347349.
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, 501509.
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, 334340.
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, 801810.
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, 5560.
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, 13801383.
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, 16741681.
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, 179187.
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, 7180.
Goldberg, D. E. ( 2005). Haemoglobin degradation. Current Topics in Microbiology and Immunology 295, 275291.
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, 47544764.
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, 919929.
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, 3056130570.
Hawdon, J. M. and Hotez, P. J. ( 1996). Hookworm: developmental biology of the infectious process. Current Opinions on Genetic Development 6, 618623.
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, 66726678.
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, 149165.
Hein, W. R. and Mackay, C. R. ( 1991). Prominence of gamma delta T cells in the ruminant immune system. Immunology Today 12, 3034.
Horton, J. ( 2003). Global anthelmintic chemotherapy programs: learning from history. Trends in Parasitology 19, 405409.
Hotez, P. J., Bethony, J., Bottazzi, M. E., Brooker, S. and Buss, P. ( 2005). Hookworm – “the great infection of mankind.” PLoS Medicine 2, e67 177181.
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, 799807.
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, 12451258.
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, 26992704.
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, 9194.
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, 935940.
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, 362368.
Jarrett, E. and Bazin, H. ( 1974). Elevation of total serum IgE in rats following helminth parasite infection. Nature 251, 613614.
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, 54505460.
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, 86428647.
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, 1523.
Kaplan, R. M. ( 2004). Drug resistance in nematodes of veterinary importance: a status report. Trends in Parasitology 20, 477481.
Klei, T. R. ( 1997). Immunological control of gastrointestinal nematode infections. Veterinary Parasitology 72, 507516.
Knox, D. P. ( 2000). Development of vaccines against gastrointestinal nematodes. Parasitology 120 (Suppl.), S4361.
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, 11291137.
Knox, D. P. and Smith, W. D. ( 2001). Vaccination against gastrointestinal nematode parasites of ruminants using gut-expressed antigens. Veterinary Parasitology 100, 2132.
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, 201210.
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, 1320.
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, 173178.
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, 6372.
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.
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, 19521961.
Loukas, A., Constant, S. L. and Bethony, J. M. ( 2005 a). Immunobiology of hookworm infection. FEMS Immunology and Medical Microbiology 43, 115124.
Loukas, A. and Prociv, P. ( 2001). Immune responses in hookworm infections. Clinical Microbiology Reviews 14, 689703.
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, 165170.
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, 125147.
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, 308314.
Meeusen, E. N. and Balic, A. ( 2000). Do eosinophils have a role in the killing of helminth parasites? Parasitology Today 16, 95101.
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, 121125.
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, 31233130.
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, 319323.
Miguel, E. A. and Kremer, M. ( 2003). Worms: identifying impacts on education and health in the presence of treatment externalities. Econometrica 72, 159217.
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, 13831390.
Miller, T. A. ( 1965 b). Persistence of immunity following double vaccination of pups with X-irradiated Ancylostoma caninum larvae. Journal of Parasitology 51, 705711.
Miller, T. A. ( 1978). Industrial development and field use of the canine hookworm vaccine. Advances in Parasitology 16, 333342.
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.
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.
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, 243248.
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, 371378.
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, 483490.
Newton, S. E. and Munn, E. A. ( 1999). The development of vaccines against gastrointestinal nematode parasites, particularly Haemonchus contortus. Parasitology Today 15, 116122.
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, 539547.
Pritchard, D. I. and Brown, A. ( 2001). Is Necator americanus approaching a mutualistic symbiotic relationship with humans? Trends in Parasitology 17, 169172.
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, 7175.
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, 617631.
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, 430438.
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, 93103.
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.
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, 42524261.
Redmond, D. L. and Knox, D. P. ( 2006). Further protection studies using recombinant forms of Haemonchus contortus cysteine proteinases. Parasite Immunology, In press.
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, 7787.
Roche, M. and Layrisse, M. ( 1966). The nature and causes of “hookworm anemia”. American journal of Tropical Medicine and Hygiene 15, 10291102.
Schallig, H. D. ( 2000). Immunological responses of sheep to Haemonchus contortus. Parasitology 120 (Suppl), S6372.
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, 293299.
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, 351357.
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, 241244.
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, 295306.
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, 271280.
Smith, W. D. and Angus, K. W. ( 1980). Haemonchus contortus: attempts to immunise lambs with irradiated larvae. Research in Veterinary Science 29, 4550.
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, 313323.
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, 19.
Smith, W. D., Smith, S. K. and Murray, J. M. ( 1994). Protection studies with integral membrane fractions of Haemonchus contortus. Parasite Immunology 16, 231241.
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, 285297.
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, 21492154.
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, 10361046.
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, 277282.
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, 7887.
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, 399404.
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, 179186.
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, 153159.
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, 223232.
Tatar, M. and Yin, C. ( 2001). Slow aging during insect reproductive diapause: why butterflies, grasshoppers and flies are like worms. Experimental Gerontology 36, 723738.
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, 348358.
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, 16411643.
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, 419426.
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, 189201.
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, 128132.
Willadsen, P. ( 2004). Anti-tick vaccines. Parasitology 129 (Suppl), S367387.
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, 14581460.
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, 417423.
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, 35603567.
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, 961967.
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, 169416951.
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, 291296.
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, 69036911.
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