A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis

 

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dc.contributor.author Nieuwenhuizen, Natalie E en_ZA
dc.contributor.author Meter, Jeanne M en_ZA
dc.contributor.author Horsnell, William G en_ZA
dc.contributor.author Hoving, J Claire en_ZA
dc.contributor.author Fick, Lizette en_ZA
dc.contributor.author Sharp, Michael F en_ZA
dc.contributor.author Darby, Matthew G en_ZA
dc.contributor.author Parihar, Suraj P en_ZA
dc.contributor.author Brombacher, Frank en_ZA
dc.contributor.author Lopata, Andreas L en_ZA
dc.date.accessioned 2016-01-11T06:53:25Z
dc.date.available 2016-01-11T06:53:25Z
dc.date.issued 2013 en_ZA
dc.identifier.citation ieuwenhuizen, N. E., Meter, J. M., Horsnell, W. G., Hoving, J. C., Fick, L., Sharp, M. F., ... & Lopata, A. L. (2012). A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis. PLoS neglected tropical diseases, 7(8), e2395. doi:10.1371/journal.pntd.0002395 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16275
dc.identifier.uri http://dx.doi.org/10.1371/journal.pntd.0002395
dc.description.abstract Background: Nematode secreted haemoglobins have unusually high affinity for oxygen and possess nitric oxide deoxygenase, and catalase activity thought to be important in protection against host immune responses to infection. In this study, we generated a monoclonal antibody (48Eg) against haemoglobin of the nematode Anisakis pegreffii, and aimed to characterize cross-reactivity of 4E8g against haemoglobins of different nematodes and its potential to mediate protective immunity against a murine hookworm infection. Methodology/Principal Findings: Immunoprecipitation was used to isolate the 4E8g-binding antigen in Anisakis and Ascaris extracts, which were identified as haemoglobins by peptide mass fingerprinting and MS/MS. Immunological cross-reactivity was also demonstrated with haemoglobin of the rodent hookworm N. brasiliensis. Immunogenicity of nematode haemoglobin in mice and humans was tested by immunoblotting. Anisakis haemoglobin was recognized by IgG and IgE antibodies of Anisakis-infected mice, while Ascaris haemoglobin was recognized by IgG but not IgE antibodies in mouse and human sera. Sequencing of Anisakis haemoglobin revealed high similarity to haemoglobin of a related marine nematode, Psuedoterranova decipiens, which lacks the four –HKEE repeats of Ascaris haemoglobin important in octamer assembly. The localization of haemoglobin in the different parasites was examined by immunohistochemistry and associated with the excretory-secretary ducts in Anisakis, Ascaris and N. brasiliensis. Anisakis haemoglobin was strongly expressed in the L3 stage, unlike Ascaris haemoglobin, which is reportedly mainly expressed in adult worms. Passive immunization of mice with 4E8g prior to infection with N. brasiliensis enhanced protective Th2 immunity and led to a significant decrease in worm burdens. Conclusion: The monoclonal antibody 4E8g targets haemoglobin in broadly equivalent anatomical locations in parasitic nematodes and enhances host immunity to a hookworm infection. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLOS Neglected Tropical Diseases en_ZA
dc.source.uri http://journals.plos.org/plosntds en_ZA
dc.subject.other Anisakis en_ZA
dc.subject.other Nematode infections en_ZA
dc.subject.other Ascaris en_ZA
dc.subject.other Enzyme-linked immunoassays en_ZA
dc.subject.other Antibodies en_ZA
dc.subject.other Oxygen en_ZA
dc.subject.other Ascaris lumbricoides en_ZA
dc.subject.other Monoclonal antibodies en_ZA
dc.title A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2013 Nieuwenhuizen et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Nieuwenhuizen, N. E., Meter, J. M., Horsnell, W. G., Hoving, J. C., Fick, L., Sharp, M. F., ... Lopata, A. L. (2013). A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis. <i>PLOS Neglected Tropical Diseases</i>, http://hdl.handle.net/11427/16275 en_ZA
dc.identifier.chicagocitation Nieuwenhuizen, Natalie E, Jeanne M Meter, William G Horsnell, J Claire Hoving, Lizette Fick, Michael F Sharp, Matthew G Darby, Suraj P Parihar, Frank Brombacher, and Andreas L Lopata "A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis." <i>PLOS Neglected Tropical Diseases</i> (2013) http://hdl.handle.net/11427/16275 en_ZA
dc.identifier.vancouvercitation Nieuwenhuizen NE, Meter JM, Horsnell WG, Hoving JC, Fick L, Sharp MF, et al. A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis. PLOS Neglected Tropical Diseases. 2013; http://hdl.handle.net/11427/16275. en_ZA
dc.identifier.ris TY - Journal Article AU - Nieuwenhuizen, Natalie E AU - Meter, Jeanne M AU - Horsnell, William G AU - Hoving, J Claire AU - Fick, Lizette AU - Sharp, Michael F AU - Darby, Matthew G AU - Parihar, Suraj P AU - Brombacher, Frank AU - Lopata, Andreas L AB - Background: Nematode secreted haemoglobins have unusually high affinity for oxygen and possess nitric oxide deoxygenase, and catalase activity thought to be important in protection against host immune responses to infection. In this study, we generated a monoclonal antibody (48Eg) against haemoglobin of the nematode Anisakis pegreffii, and aimed to characterize cross-reactivity of 4E8g against haemoglobins of different nematodes and its potential to mediate protective immunity against a murine hookworm infection. Methodology/Principal Findings: Immunoprecipitation was used to isolate the 4E8g-binding antigen in Anisakis and Ascaris extracts, which were identified as haemoglobins by peptide mass fingerprinting and MS/MS. Immunological cross-reactivity was also demonstrated with haemoglobin of the rodent hookworm N. brasiliensis. Immunogenicity of nematode haemoglobin in mice and humans was tested by immunoblotting. Anisakis haemoglobin was recognized by IgG and IgE antibodies of Anisakis-infected mice, while Ascaris haemoglobin was recognized by IgG but not IgE antibodies in mouse and human sera. Sequencing of Anisakis haemoglobin revealed high similarity to haemoglobin of a related marine nematode, Psuedoterranova decipiens, which lacks the four –HKEE repeats of Ascaris haemoglobin important in octamer assembly. The localization of haemoglobin in the different parasites was examined by immunohistochemistry and associated with the excretory-secretary ducts in Anisakis, Ascaris and N. brasiliensis. Anisakis haemoglobin was strongly expressed in the L3 stage, unlike Ascaris haemoglobin, which is reportedly mainly expressed in adult worms. Passive immunization of mice with 4E8g prior to infection with N. brasiliensis enhanced protective Th2 immunity and led to a significant decrease in worm burdens. Conclusion: The monoclonal antibody 4E8g targets haemoglobin in broadly equivalent anatomical locations in parasitic nematodes and enhances host immunity to a hookworm infection. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pntd.0002395 DP - University of Cape Town J1 - PLOS Neglected Tropical Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis TI - A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis UR - http://hdl.handle.net/11427/16275 ER - en_ZA


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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.