title: Examining the cross-reactivity and neutralization mechanisms of a panel of mAbs against adeno-associated virus serotypes 1 and 5.
abstract: Neutralizing antibodies play a central role in the prevention and clearance of viral infections, but can be detrimental to the use of viral capsids for gene delivery. Antibodies present a major hurdle for ongoing clinical trials using adeno-associated viruses (AAVs); however, relatively little is known about the antigenic epitopes of most AAV serotypes or the mechanism(s) of antibody-mediated neutralization. We developed panels of AAV mAbs by repeatedly immunizing mice with AAV serotype 1 (AAV1) capsids, or by sequentially immunizing with AAV1 followed by AAV5 capsids, in order to examine the efficiency and mechanisms of antibody-mediated neutralization. The antibodies were not cross-reactive between heterologous AAV serotypes except for a low level of recognition of AAV1 capsids by the AAV5 antibodies, probably due to the initial immunization with AAV1. The neutralization efficiency of different IgGs varied and Fab fragments derived from these antibodies were generally poorly neutralizing. The antibodies appeared to display various alternative mechanisms of neutralization, which included inhibition of receptor-binding and interference with a post-attachment step.
authors.affiliation: Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Carole E
authors.initials: CE
authors.lastname: Harbison
authors.affiliation: Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Weichert
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Brittney L
authors.initials: BL
authors.lastname: Gurda
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, US National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Chiorini
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Mavis
authors.initials: M
authors.lastname: Agbandje-McKenna
authors.affiliation: Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Parrish
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D003429:Cross Reactions; D000229:Dependovirus / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G
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