Anti-adeno-associated viral vector (AAV) neutralizing antibodies (NAbs) can ablate efficacy of transgene expression following intravenous vector administration. This observation in both preclinical and clinical trials has led to exclusion of NAb-positive patients from receiving AAV gene therapy. AAV drug development includes selection of capsids with lower NAb seroprevalence that also possess other favorable traits. Often a limited number of healthy volunteers are screened to gauge NAb seroprevalence. However, limited data sets can be biased leading to inaccurate estimates of NAb incidence. In this study, we evaluated AAV NAbs against a panel of vectors among healthy donors within the United States. While the overall seroprevalence against most AAVs was lower, we did observe increased NAb incidence among black and Hispanic donors. These findings of increased NAb seroprevalence among the minority races were confirmed in a second set of donors who also demonstrated higher seroprevalence among these races. Interracial- and intraracial differences within genders were also observed among donors. The increased incidence of AAV NAb among racial minorities was unexpected. Our findings underscore the need for removing bias in sample data sets and evaluating seroprevalence within the patient population while selecting capsids.

中文翻译：

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美国少数族裔中抗腺相关病毒载体中和抗体的血清阳性率较高

抗腺相关病毒载体 (AAV) 中和抗体 (NAb) 可以消除静脉内载体给药后转基因表达的功效。临床前和临床试验中的这一观察结果导致 NAb 阳性患者被排除在接受 AAV 基因治疗之外。AAV 药物开发包括选择具有较低 NAb 血清阳性率且还具有其他有利特征的衣壳。通常对有限数量的健康志愿者进行筛查以评估 NAb 血清阳性率。然而，有限的数据集可能存在偏差，导致对 NAb 发病率的估计不准确。在这项研究中，我们针对美国健康供体中的一组载体评估了 AAV NAb。虽然针对大多数 AAV 的总体血清阳性率较低，但我们确实观察到黑人和西班牙裔捐赠者的 NAb 发病率增加。这些少数种族中NAb血清阳性率增加的发现在第二组供体中得到证实，他们也表现出这些种族中更高的血清阳性率。在捐赠者中也观察到了性别内的种族间和种族内差异。少数族裔中 AAV NAb 发病率的增加是出乎意料的。我们的研究结果强调了在选择衣壳时需要消除样本数据集中的偏差并评估患者群体中的血清阳性率。