Prevalence of Neutralizing Antibodies Against AAV Serotypes 2 and 9 in Healthy Participants from Multiple Centers Across China and Patients with DMD/BMD

Overview

Journal Hum Gene Ther

Specialties Genetics
Pharmacology

Date 2024 Nov 28

PMID 39607725

Authors

Xuzhen Qin

Huan Li

Huiying Zhao

Kuanhui Xiang

Shihui Liu

Ruolin Lou

Peng Liu

Yi Dai

Chuanxin Wang

Shuyang Zhang

Affiliations

Soon will be listed here.

Abstract

To facilitate adeno-associated virus (AAV)-mediated gene therapy in China, we conducted a study on the distribution of AAV-neutralizing antibodies (NAbs) in healthy subjects and in patients with Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD). A total of 352 healthy adult controls (ACs) from a national multicenter study, 100 schoolchild controls (SCs), and 281 patients with DMD/BMD from Peking Union Medical College Hospital were enrolled in this study. Cell-based inhibition assays were applied, and serum samples demonstrating 50% inhibition of infection were considered positive. The seroprevalence of AAV2 and AAV9 NAbs among the 733 participants was 86.1% and 56.3%, respectively. The AAV2 NAbs and AAV9 NAbs positivity rates in the AC, SC, and DMD/BMD groups were 97.4%/86.6%, 100.0%/17.0%, and 66.9%/32.4%, respectively. The seroprevalence of AAV NAbs gradually increased with age, especially in AAV9 NAbs. Females tended to have higher positivity rate than males. Over 85% of ACs had overlapping AAV9 and AAV2 infection. However, being positive for only AAV2 NAbs in the SC group was common, and 30.6% of patients with DMD/BMD were negative for both AAV2 and AAV9 NAbs. Our findings reveal that a significant proportion of patients with DMD/BMD were negative for AAV2 and AAV9 NAbs, which is the population that is most amenable to being treated with gene therapy.

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