Abstract:
Adaptive immunity to viral infections requires time to neutralize and clear viruses to resolve infection. Fast growing and pathogenic viruses are quickly established, are highly transmissible and cause significant disease burden making it difficult to mount effective responses, thereby prolonging infection. Antibody-based passive immunotherapies can provide initial protection during acute infection, assist in mounting an adaptive immune response, or provide protection for those who are immune suppressed or immune deficient. Historically, plasma-derived antibodies have demonstrated some success in treating diseases caused by viral pathogens; nonetheless, limitations in access to product and antibody titer reduce success of this treatment modality. Monoclonal antibodies (mAbs) have proven an effective alternative, as it is possible to manufacture highly potent and specific mAbs against viral targets on an industrial scale. As a result, innovative technologies to discover, engineer and manufacture specific and potent antibodies have become an essential part of the first line of treatment in pathogenic viral infections. However, a mAb targeting a specific epitope will allow escape variants to outgrow, causing new variant strains to become dominant and resistant to treatment with that mAb. Methods to mitigate escape have included combining mAbs into cocktails, creating bi-specific or antibody drug conjugates but these strategies have also been challenged by the potential development of escape mutations. New technologies in developing antibodies made as recombinant polyclonal drugs can integrate the strength of poly-specific antibody responses to prevent mutational escape, while also incorporating antibody engineering to prevent antibody dependent enhancement and direct adaptive immune responses.
摘要:
对病毒感染的适应性免疫需要时间来中和和清除病毒以解决感染。快速生长和致病病毒迅速建立,是高度传染性的,并造成巨大的疾病负担,使得难以进行有效的反应,从而延长感染。基于抗体的被动免疫疗法可以在急性感染期间提供初始保护,协助进行适应性免疫反应,或为免疫抑制或免疫缺陷的人提供保护。历史上,血浆衍生的抗体已证明在治疗由病毒病原体引起的疾病方面取得了一些成功;尽管如此,获得产品和抗体滴度的限制降低了这种治疗方式的成功率.单克隆抗体(mAb)已被证明是一种有效的替代品,因为有可能在工业规模上制造针对病毒靶标的高效和特异性mAb。因此,要发现的创新技术,设计和制造特异性和强效抗体已成为致病性病毒感染一线治疗的重要组成部分。然而,针对特定表位的mAb将允许逃逸变体生长,导致新的变异菌株成为显性菌株,并对该mAb的治疗产生抗性。减轻逃逸的方法包括将单克隆抗体混合成鸡尾酒,创建双特异性或抗体药物缀合物,但这些策略也受到逃避突变的潜在发展的挑战。开发作为重组多克隆药物的抗体的新技术可以整合多特异性抗体反应的强度,以防止突变逃逸,同时还纳入抗体工程以防止抗体依赖性增强和直接适应性免疫反应。