Antibody-based PrEP and Cross-reactivity

AIDS Research and Human RetrovirusesVol. 30, No. S1 Glycans and Antibody Effector FunctionsFree AccessAntibody-based PrEP and Cross-reactivityKevin J. Whaley, Steve Hume, and Larry ZeitlinKevin J. WhaleyMapp Biopharmaceutical, San Diego, CA, United StatesSearch for more papers by this author, Steve HumeKentucky Bioprocessing, Inc., Owensboro, KY, United StatesSearch for more papers by this author, and Larry ZeitlinMapp Biopharmaceutical, Inc., San Diego, CA, United StatesSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5457.abstractAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail P34.10Background: Broadly neutralizing antibodies (bNAbs) are being developed for topical and systemic pre-exposure prophylaxis. Since some bNAbs (e.g. 4E10) have been reported to interact with non-viral epitopes, the cross-reactivity of bNAbs is an important safety parameter to be documented in regulatory submissions. The objective of this study was to determine the cross-reactivity of Nicotiana (-N) manufactured anti-HIV bNAbs 4E10-N and VRC01-N, and anti-HSV glycoprotein D bNAb HSV8-N with cryosections of human tissues.Methods: In order to detect binding, the antibodies were biotinylated and applied to cryosections of normal human tissues (3 donors per tissue) at two concentrations (2-20 μg/ml). Commercially available Synagis was biotinylated and used as a control. The study was GLP compliant.Results: 4E10-N variably stained a variety of tissue elements in the human tissue panel. VRC01-N also produced staining of tissue elements; however, the staining with VRC01-N was generally present in fewer tissues and with reduced intensity and frequency. No staining with HSV8-N or Synagis was observed in the human tissue panel examined.Conclusions: The majority of observed staining was cytoplasmic in nature, which is of little toxicologic concern since the cytoplasmic compartment is generally considered to be inaccessible to antibodies administered in vivo. The toxicologic concern for the observed staining of extracellular elements in selected tissues with 4E10-N and VRC01-N is unknown. Since no staining was observed with HSV8-N the binding of VRC01-N cannot be attributed to the Nictotiana-based manufacturing system.FiguresReferencesRelatedDetails Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Kevin J. Whaley, Steve Hume, and Larry Zeitlin.Antibody-based PrEP and Cross-reactivity.AIDS Research and Human Retroviruses.Oct 2014.A210-A211.http://doi.org/10.1089/aid.2014.5457.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download