@article{a18fe621e26b47efb203ad94228d759f,
title = "Characterization of glycan determinants that mediate recognition of the major Wuchereria bancrofti circulating antigen by diagnostic antibodies",
abstract = "The Global Program to Eliminate Lymphatic Filariasis (GPELF) relies heavily on a rapid diagnostic test (RDT) to a Wuchereria bancrofti circulating filarial antigen (Wb-CFA) to identify endemic areas and for determining when mass drug administration can stop. The antigen contains a carbohydrate epitope that is recognized by monoclonal antibody AD12. Og4C3, a monoclonal antibody that is used in a commercial ELISA for Wb-CFA recognizes the same moiety. Despite its diagnostic importance, little is known about the structure and function of this “AD12 epitope”. It is also present on other W. bancrofti glycoproteins and on glycoproteins of other filarial worms, but such antigens are not detected in the sera of individuals with most other filarial infections. We report here functional and biochemical analyses that shed light on the interaction between filarial glycoproteins and AD12 and/or Og4C3. Binding of these monoclonal antibodies to a mammalian glycan array suggests the reactive moiety has structural similarity to terminal β-D-glucuronic acid in a 1–3 linkage to other hexoses. However, sera collected from individuals with patent W. bancrofti infection had very low or undetectable serum antibodies to the GlcA-containing array glycans. Unlike other filarial glycoproteins, the Wb-CFA is relatively resistant to protease digestion by pronase and trypsin and completely resistant to the mucinase O-sialoglycoprotein endopeptidase (OSGE). The protease resistance of the Wb-CFA may contribute to its consistent detection in Wb-infected sera.",
keywords = "Brugia malayi, Glucuronic acid, Loiasis, Lymphatic filariasis, Rapid diagnostic test, Wuchereria bancrofti",
author = "Hertz, {Marla I.} and Amy Rush and Nutman, {Thomas B.} and Weil, {Gary J.} and Sasisekhar Bennuru and Budge, {Philip J.}",
note = "Funding Information: This work was supported by the National Institute for Allergy and Infectious Disease (NIAID) [grant number K08AI121422 (PJB)] and an NIH Loan Repayment Programs (NIAID) award (PJB). This work was also supported, in part, by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and by the Foundation for Barnes-Jewish Hospital. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding Information: This work was supported by the National Institute for Allergy and Infectious Disease (NIAID) [grant number K08AI121422 (PJB)] and an NIH Loan Repayment Programs (NIAID) award (PJB). This work was also supported, in part, by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and by the Foundation for Barnes-Jewish Hospital. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding Information: This study utilized the NIH / NIGMS Biomedical Mass Spectrometry Resource at Washington University in St. Louis, MO, which is supported by National Institutes of Health / National Institute of General Medical Sciences Grant # 8P41GM103422. We are appreciative of the guidance and advice from the members of the Nutman and Weil labs. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = nov,
doi = "10.1016/j.molbiopara.2020.111317",
language = "English",
volume = "240",
journal = "Molecular and Biochemical Parasitology",
issn = "0166-6851",
}