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Toward developing a human hookworm vaccine, we expressed both wild\u2010type (\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101\n                    <jats:sub>wt<\/jats:sub>\n                    ) and mutant (\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101\n                    <jats:sub>mut<\/jats:sub>\n                    \u2014mutagenesis of the catalytic aspartic acids) forms of\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101 from the human hookworm,\n                    <jats:italic>Necator americanus.<\/jats:italic>\n                    Refolded\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101\n                    <jats:sub>wt<\/jats:sub>\n                    was catalytically active, and\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101\n                    <jats:sub>mut<\/jats:sub>\n                    was catalytically inactive but still bound substrates. Vaccination of canines with\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101\n                    <jats:sub>mut<\/jats:sub>\n                    and heterologous challenge with\n                    <jats:italic>A. caninum<\/jats:italic>\n                    resulted in significantly reduced parasite egg burdens (\n                    <jats:italic>P<\/jats:italic>\n                    =0.034) and weight loss (\n                    <jats:italic>P<\/jats:italic>\n                    =0.022). Vaccinated dogs also had less gut pathology, fewer adult worms, and reduced blood loss compared to controls but these did not reach statistical significance. Vaccination with\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101\n                    <jats:sub>mut<\/jats:sub>\n                    induced antibodies that bound the native enzyme in the parasite gut and neutralized enzymatic activity of\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101\n                    <jats:sub>wt<\/jats:sub>\n                    and APR\u20101 orthologues from three other hookworm species that infect humans. IgG1 against\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101\n                    <jats:sub>mut<\/jats:sub>\n                    was the most prominently detected antibody in sera from people resident in high\u2010transmission areas for\n                    <jats:italic>N. americanus<\/jats:italic>\n                    , indicating that natural boosting may occur in exposed humans.\n                    <jats:italic>Na<\/jats:italic>\n                    \u2010APR\u20101\n                    <jats:sub>mut<\/jats:sub>\n                    is now a lead antigen for the development of an antihematophagy vaccine for human hookworm disease.\u2014Pearson, M. S., Bethony, J. M., Pickering, D. A., de Oliveira, L. M., Jariwala, A., Santiago, H., Miles, A. P., Zhan, B., Jiang, D., Ranjit, N., Mulvenna, J., Tribolet, L., Plieskatt, J., Smith, T., Bottazzi, M. E., Jones, K., Keegan, B., Hotez, P. J., Loukas, A. An enzymatically inactivated hemoglobinase from\n                    <jats:italic>Necator americanus<\/jats:italic>\n                    induces neutralizing antibodies against multiple hookworm species and protects dogs against heterologous hookworm infection.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    23, 3007\u20133019 (2009).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.09-131433","type":"journal-article","created":{"date-parts":[[2009,4,20]],"date-time":"2009-04-20T21:10:35Z","timestamp":1240261835000},"page":"3007-3019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["An enzymatically inactivated hemoglobinase from\n                    <i>Necator americanus<\/i>\n                    induces neutralizing antibodies against multiple hookworm species and protects dogs against heterologous hookworm infection"],"prefix":"10.1096","volume":"23","author":[{"given":"Mark S.","family":"Pearson","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases Queensland Institute of Medical Research and The Australian Centre for Vaccine Development Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Bethony","sequence":"additional","affiliation":[{"name":"Department of Microbiology Immunology and Tropical Medicine George Washington University Medical Center Washington, District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren A.","family":"Pickering","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Queensland Institute of Medical Research and The Australian Centre for Vaccine Development Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana M.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Microbiology Immunology and Tropical Medicine George Washington University Medical Center Washington, District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar","family":"Jariwala","sequence":"additional","affiliation":[{"name":"Department of Microbiology Immunology and Tropical Medicine George Washington University Medical Center Washington, District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helton","family":"Santiago","sequence":"additional","affiliation":[{"name":"Department of Microbiology Immunology and Tropical Medicine George Washington University Medical Center Washington, District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron 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