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

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dc.contributor.authorNieuwenhuizen, Natalie Een_ZA
dc.contributor.authorMeter, Jeanne Men_ZA
dc.contributor.authorHorsnell, William Gen_ZA
dc.contributor.authorHoving, J Claireen_ZA
dc.contributor.authorFick, Lizetteen_ZA
dc.contributor.authorSharp, Michael Fen_ZA
dc.contributor.authorDarby, Matthew Gen_ZA
dc.contributor.authorParihar, Suraj Pen_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.contributor.authorLopata, Andreas Len_ZA
dc.date.accessioned2016-01-11T06:53:25Z
dc.date.available2016-01-11T06:53:25Z
dc.date.issued2013en_ZA
dc.description.abstractBackground: 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.identifier.apacitationNieuwenhuizen, 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/11427/16275en_ZA
dc.identifier.chicagocitationNieuwenhuizen, 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/11427/16275en_ZA
dc.identifier.citationieuwenhuizen, 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.0002395en_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
dc.identifier.urihttp://hdl.handle.net/11427/16275
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pntd.0002395
dc.identifier.vancouvercitationNieuwenhuizen 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.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.holder© 2013 Nieuwenhuizen et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLOS Neglected Tropical Diseasesen_ZA
dc.source.urihttp://journals.plos.org/plosntdsen_ZA
dc.subject.otherAnisakisen_ZA
dc.subject.otherNematode infectionsen_ZA
dc.subject.otherAscarisen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherAntibodiesen_ZA
dc.subject.otherOxygenen_ZA
dc.subject.otherAscaris lumbricoidesen_ZA
dc.subject.otherMonoclonal antibodiesen_ZA
dc.titleA cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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