{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:07:33Z","timestamp":1792523253117,"version":"4.5.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>\n                    Recombinant adeno-associated virus (rAAV) vectors are a promising platform for\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    gene therapy. The presence of neutralizing antibodies (Nab) against AAV capsids decreases cell transduction efficiency and is a common exclusion criterion for participation in clinical trials. Novel engineered capsids are being generated to improve gene delivery to the target cells and facilitate success of clinical trials; however, the prevalence of antibodies against such capsids remains largely unknown. We therefore assessed the seroprevalence of antibodies against a novel synthetic liver-tropic capsid AAV-LK03. We measured seroprevalence of immunoglobulin (Ig)G (i.e., neutralizing and nonneutralizing) antibodies and Nab to AAV-LK03 in a cohort of 323 UK patients (including 260 pediatric) and 52 juvenile rhesus macaques. We also performed comparative analysis of seroprevalence of Nab against wild-type AAV8 and AAV3B capsids. Overall IgG seroprevalence for AAV-LK03 was 39% in human samples. The titer increased with age. Prevalence of Nab was 23%, 35%, and 18% for AAV-LK03, AAV3B, and AAV8, respectively, with the lowest seroprevalence between 3 and 17 years of age for all serotypes. Presence of Nab against AAV-LK03 decreased from 36% in the youngest cohort (birth to 6 months) to 7% in older primary school-age children (9\u201311 years) and then progressively increased to 54% in late adulthood. Cross-reactivity between serotypes was &gt;60%. Nab seroprevalence in macaques was 62%, 85%, and 40% for AAV-LK03, AAV3B, and AAV8, respectively. When planning for AAV gene therapy clinical trials, knowing the seropositivity of the target population is critical. In the population studied, AAV seroprevalence for AAV serotypes tested was low. However, high cross-reactivity between AAV serotypes remains a barrier for re-injection. Shifts in Nab seroprevalence during the first decade need to be confirmed by longitudinal studies. This possibility suggests that pediatric patients could respond differently to AAV therapy according to age. If late childhood is an ideal age window, intervention at an early age when maternal Nab levels are high may be challenging. Nab-positive children excluded from trials could be rescreened for eligibility at regular intervals because this status may change.\n                  <\/jats:p>","DOI":"10.1089\/hum.2018.098","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T06:33:39Z","timestamp":1532068419000},"page":"79-87","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":78,"title":["Age-Related Seroprevalence of Antibodies Against AAV-LK03 in a UK Population Cohort"],"prefix":"10.1177","volume":"30","author":[{"given":"Dany P.","family":"Perocheau","sequence":"first","affiliation":[{"name":"Genetics and Genomic Medicine Programme, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom."},{"name":"Gene Transfer Technology Group, Institute for Women's Health, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon C.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Gene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney and Sydney Children's Hospital Network, Westmead, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhee","family":"Lee","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Medicine Programme, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom."},{"name":"Gene Transfer Technology Group, Institute for Women's Health, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Antinao Diaz","sequence":"additional","affiliation":[{"name":"Gene Transfer Technology Group, Institute for Women's Health, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon N.","family":"Waddington","sequence":"additional","affiliation":[{"name":"Gene Transfer Technology Group, Institute for Women's Health, University College London, London, United Kingdom."},{"name":"Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witswatersrand, Johannesburg, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Gilmour","sequence":"additional","affiliation":[{"name":"Clinical Immunology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Eaglestone","sequence":"additional","affiliation":[{"name":"Translational Research Office, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leszek","family":"Lisowski","sequence":"additional","affiliation":[{"name":"Gene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney and Sydney Children's Hospital Network, Westmead, Australia."},{"name":"Translational Vectorology Group, Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, Australia."},{"name":"Military Institute of Hygiene and Epidemiology, The Biological Threats Identification and Countermeasure Centre, Pu\u0142awy, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Thrasher","sequence":"additional","affiliation":[{"name":"Clinical Immunology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom."},{"name":"Infection, Immunity and Inflammation Programme, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian E.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Gene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney and Sydney Children's Hospital Network, Westmead, Australia."},{"name":"Discipline of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Westmead, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gissen","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Medicine Programme, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom."},{"name":"MRC Laboratory for Molecular Biology, University College London, London, United Kingdom."},{"name":"Metabolic Medicine Department, Great Ormond Street Hospital for Children NHS 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