Botulinum neurotoxins (BoNTs) are proteins produced by bacteria of the Clostridium family. Upon oral ingestion, BoNT causes the neuroparalytic syndrome botulism. There are seven serotypes of BoNT (serotypes A-G); BoNT-A and BoNT-B are the botulinum toxin serotypes utilized for therapeutic applications. Treatment with BoNT injections is used to manage chronic medical conditions across multiple indications. As with other biologic drugs, immunogenicity after long-term treatment with BoNT formulations may occur, and repeated use can elicit antibody formation leading to clinical nonresponsiveness. Thus, approaching BoNT treatment of chronic conditions with therapeutic formulations that minimize stimulating the host immune response while balancing patient responsiveness to therapy is ideal. Immunogenicity is a clinical limitation in many settings that use biologic drugs for treatment, and clinically relevant immunogenicity reduction has been achieved through engineering smaller protein constructs and reducing unnecessary formulation components. A similar approach has influenced the evolution of BoNT formulations. Three BoNT-A products and one BoNT-B product have been approved by the Food and Drug Administration (FDA) for therapeutic use: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB; a fourth BoNT-A product, daxibotulinumtoxinA, is currently under regulatory review. Additionally, prabotulinumtoxinA is a BoNT-A product that has been approved for aesthetic indications but not therapeutic use. Here, we discuss the preclinical and clinical immunogenicity data that exist within the scientific literature and provide a perspective for considering immunogenicity as a key factor in choice of BoNT formulation.

肉毒杆菌神经毒素 (BoNT) 是由梭状芽胞杆菌产生的蛋白质家庭。口服后，BoNT 会导致神经麻痹综合征肉毒杆菌中毒。BoNT有七种血清型（血清型AG）；BoNT-A 和 BoNT-B 是用于治疗应用的肉毒杆菌毒素血清型。肉毒毒素注射治疗用于管理多种适应症的慢性疾病。与其他生物药物一样，长期使用 BoNT 制剂治疗后可能会产生免疫原性，重复使用会引起抗体形成，导致临床无反应。因此，理想的方法是使用能够最大限度地减少对宿主免疫反应的刺激同时平衡患者对治疗的反应性的治疗配方来治疗慢性疾病。在许多使用生物药物进行治疗的环境中，免疫原性是一个临床限制，通过设计更小的蛋白质构建体和减少不必要的制剂成分，已经实现了临床相关免疫原性的降低。类似的方法影响了 BoNT 制剂的演变。三种 BoNT-A 产品和一种 BoNT-B 产品已获得美国食品和药物管理局 (FDA) 的治疗用途批准：onabotulinumtoxinA、abobotulinumtoxinA、incobotulinumtoxinA 和 rimabotulinumtoxinB；第四种 BoNT-A 产品 daxibotulinumtoxinA 目前正在接受监管审查。此外，前肉毒毒素 A 是一种肉毒毒素 A 产品，已被批准用于美容适应症，但未获批准用于治疗用途。这里，