Abstract Number: LPB0022
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia Gene Therapy
Background: Adeno‐associated virus (AAV)‐mediated gene therapy may provide durable protection from bleeding events and reduced treatment burden to people with hemophilia A (PwHA). However, pre-existing immunity against AAV may limit treatment success. Global data on the prevalence of AAV serotypes are limited.
Aims: We determined the prevalence of pre-existing immunity against AAV2, AAV5, AAV6, AAV8, and rh10 capsids among PwHA from 9 countries.
Methods: BMN 270-901 was a prospective study conducted in PwHA in Brazil, France, Germany, Italy, Japan, Russia, South Africa, the UK, and the USA. Plasma samples were collected from participants who provided informed consent. Antibodies against each serotype were detected using validated, electrochemiluminescent‐based enzyme-linked immunosorbent assays. To evaluate changes in antibody titers over time, 20% of participants were retested at 3 and 6 months.
Results: The study enrolled 546 participants: 478 adults (aged ≥18 years) and 68 adolescents (<18 years). Global seroprevalence of antibodies on day 1 are displayed in Table 1.
AAV Serotype | Global | Brazil | France | Germany | Italy | Japan | Russia | South Africa | UK | USA |
AAV2 +/total (%) | 300/513 (58.5%) | N/A | 52/86 (60.5%) | 43/89 (48.3%) | 9/20 (45.0%) | 36/83 (43.4%) | 58/91 (63.7%) | 53/56 (94.6%) | 11/17 (64.7%) | 38/71 (53.5%) |
AAV5 +/total (%) | 188/540 (34.8%) | 7/26 (26.9%) | 32/86 (37.2%) | 25/89 (28.1%) | 8/20 (40.0%) | 25/84 (29.8%) | 42/91 (46.2%) | 29/56 (51.8%) | 1/17 (5.9%) |
19/71 (26.8%) |
AAV6 +/total (%) | 250/513 (48.7%) | N/A | 47/86 (54.7%) | 39/89 (43.8%) | 8/20 (40.0%) | 26/83 (31.3%) | 51/91 (56.0%) | 45/56 (80.4%) | 7/17 (41.2%) | 27/71 (38.0%) |
AAV8 +/total (%) | 234/513 (45.6%) | N/A | 39/86 (45.3%) | 38/89 (42.7%) | 8/20 (40.0%) | 32/83 (38.6%) | 49/91 (53.8%) | 39/56 (69.6%) | 7/17 (41.2%) | 22/71 (31.0%) |
rh10 +/total (%) | 236/513 (46.0%) | N/A | 45/86 (52.3%) | 33/89 (37.1%) | 10/20 (50.0%) | 25/83 (30.1%) | 48/91 (52.7%) | 41/56 (73.2%) | 9/17 (52.9%) | 25/71 (35.2%) |
Data are shown for participants with non-missing assessments. +, positive; AAV, adeno‐associated virus; N/A, not available. |
Table 1: Global seroprevalence of antibodies on day 1
Considerable geographic variability was observed in the prevalence of pre‐existing antibodies against each serotype, but the percentage of participants positive for AAV5 was consistently the lowest among serotypes and across the countries studied. A greater percentage of adult participants were positive for AAV5 antibodies (36%) when compared with adolescents (29%). Comparative analyses of AAV serostatus in non-hemophilic individuals in select countries showed similar rates of seropositivity, as would be expected for viruses endemic to the human population. Serostatus and antibody titer were generally stable over the 6-month sampling period.
Conclusions: Among PwHA, pre-existing immunity against AAV serotypes varied across serotypes and regions, but global seropositivity was lowest for AAV5 and highest for AAV2. As clinical trials of AAV-mediated gene therapies progress, the presence of antibodies against the various AAV serotypes may become an increasingly important eligibility consideration.
To cite this abstract in AMA style:
Klamroth R, Hayes G, Andreeva T, Suzuki T, Hardesty B, Shima M, Pollock T, Slev P, Oldenburg J, C Ozelo M, Castet S-, Mahlangu J, Peyvandi F, Kazmi R, D Leavitt A, Callaghan M, Pan-Petesch B, Quon D, Li M, Wong WY. Global Seroprevalence of Pre-existing Immunity against AAV Serotypes in People with Hemophilia A [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/global-seroprevalence-of-pre-existing-immunity-against-aav-serotypes-in-people-with-hemophilia-a/. Accessed September 27, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/global-seroprevalence-of-pre-existing-immunity-against-aav-serotypes-in-people-with-hemophilia-a/