title: Suppression of Immune Response to Adenovirus Serotype 5 Vector by Immunization with Peptides Containing an MHC Class II Epitope and a Thio-Oxidoreductase Motif.
abstract: The main obstacle to viral vector-mediated gene therapy remains the elicitation of an immune response to the vector, resulting in clearance of transgene and resistance to further transgenesis. Specific antibody production contributes to such immune responses. A single class II-restricted epitope of adenovirus serotype 5 (Ad5) vector hexon-6 capsid protein containing a thiol-oxidoreductase motif was used in an attempt to prevent specific antibody production in response to Ad5 vectors. We demonstrate here that such immunization carried out before intravenous administration of Ad5 vectors prevents antibody production to the ensemble of Ad5 vector proteins in both BALB/c and C57BL/6 mice. The antibody response to Ad5 is dependent on innate immune activation, seemingly involving natural killer T (NKT) cells. We observed that immunization with a class II-restricted Ad5 peptide prevents such NKT cell activation. Increased transgenesis and prolonged transgene expression result from such immunization, providing a simple protocol for improving gene therapy.
authors.affiliation: 1 Center for Molecular and Vascular Biology, University of Leuven , Leuven, Belgium.|2 Imcyse SA, Leuven, Belgium.
authors.forename: Wei
authors.initials: W
authors.lastname: Miao
authors.affiliation: 2 Imcyse SA, Leuven, Belgium.
authors.forename: Roxana
authors.initials: R
authors.lastname: Roohi Ahangarani
authors.affiliation: 2 Imcyse SA, Leuven, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Carlier
authors.affiliation: 2 Imcyse SA, Leuven, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Vander Elst
authors.affiliation: 1 Center for Molecular and Vascular Biology, University of Leuven , Leuven, Belgium.|2 Imcyse SA, Leuven, Belgium.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Saint-Remy
mesh_terms: D000256:Adenoviridae / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D020816:Amino Acid Motifs / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology*; D056724:Immunity, Humoral; D007113:Immunity, Innate; D007114:Immunization; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C018315:hexon capsid protein, Adenovirus; D010088:Oxidoreductases