By a News Reporter-Staff News Editor at Hematology Week -- New research on Immunology is the subject of a report. According to news originating from Reno, Nevada, by NewsRx correspondents, research stated, "AAV vectors have shown great promise for clinical gene therapy (GT), but pre-existing human immunity against the AAV capsid often limits transduction. Thus, testing promising AAV-based GT approaches in an animal model with similar pre-existing immunity could better predict clinical outcome."
Our news journalists obtained a quote from the research from the University of Nevada, "Sheep have long been used for basic biological and preclinical studies. Moreover, we have re-established a line of sheep with severe hemophilia A (HA). Given the impetus to use AAV-based GT to treat hemophilia, we characterized the pre-existing ovine humoral immunity to AAV. ELISA revealed naturally-occurring antibodies to AAV1, AAV2, AAV5, AAV6, AAV8, and AAV9. For AAV2, AAV8, and AAV9 these inhibit transduction in a luciferase-based neutralization assay. Epitope mapping identified peptides that were common to the capsids of all AAV serotypes tested (AAV2, AAV5, AAV8 and AAV9), with each animal harboring antibodies to unique and common capsid epitopes. Mapping using X-ray crystallographic AAV capsid structures demonstrated that these antibodies recognized both surface epitopes and epitopes located within regions of the capsid that are internal or buried in the capsid structure. These results suggest that sheep harbor endogenous AAV, which induces immunity to both intact capsid and to capsid epitopes presented following proteolysis during the course of infection."
According to the news editors, the research concluded: "Their clinically relevant physiology and the presence of naturally-occurring antibodies to multiple AAV serotypes collectively make sheep a unique model in which to study GT for HA, and other diseases, and develop strategies to circumvent the clinically important barrier of pre-existing AAV immunity."
For more information on this research see: Characterization of naturally-occurring humoral immunity to AAV in sheep. Plos One, 2013;8(9):e75142. (Public Library of Science - www.plos.org; Plos One - www.plosone.org)
The news correspondents report that additional information may be obtained from J. Tellez, Dept. of Animal Biotechnology, University of Nevada, Reno, Nevada, United States. Additional authors for this research include K. Van Vliet, Y.S. Tseng, J.D. Finn, N. Tschernia, G. Almeida-Porada, V.R. Arruda, M. Agbandje-McKenna and C.D Porada (see also Immunology).
Keywords for this news article include: Reno, Antibodies, Antigens, Nevada, Epitopes, Immunology, United States, Blood Proteins, Immunoglobulins, North and Central America.
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