Popkov Mikhail, Gonzalez Beatriz, Sinha Subhash C, Barbas Carlos F
The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4378-83. doi: 10.1073/pnas.0900147106. Epub 2009 Mar 2.
The ability to instantly create a state of immunity as achieved in the passive transfer of hyperimmune globulin has had a tremendous impact on public health. Unlike passive immunization, active immunization, which is the foundation of vaccinology, is an anticipatory strategy with inherent limitations. Here we show that elements of active and passive immunization can be combined to create an effective chemistry-driven approach to vaccinology. Reactive immunization was used to create a reservoir of covalent polyclonal antibodies in 3 mouse strains that were subsequently engrafted with syngeneic CT26 colon or B16F10 melanoma tumors. Upon administration of designed integrin alpha(v)beta(3) and alpha(v)beta(5) adapter ligands, the induced covalent polyclonal antibodies self-assembled with the adapter ligands and the animals mounted an instant, chemically programmed, polyclonal response against the implanted tumors. Significant therapeutic responses were observed without recourse to adjuvant therapy. The chemically programmed immune responses were driven by antibody-dependent cellular cytotoxicity and complement-directed cytotoxicity. We suggest that this type of chemistry-driven approach to vaccinology is underexplored and may provide routes to vaccines to protect against diseases that have proven intractable to biology-driven vaccine approaches.
超免疫球蛋白被动转移所实现的即时产生免疫状态的能力对公共卫生产生了巨大影响。与被动免疫不同，主动免疫作为疫苗学的基础，是一种具有固有局限性的前瞻性策略。在此，我们表明主动免疫和被动免疫的要素可以结合起来，创造一种有效的化学驱动疫苗学方法。反应性免疫用于在3种小鼠品系中创建共价多克隆抗体库，随后将同基因的CT26结肠癌或B16F10黑色素瘤肿瘤移植到这些小鼠体内。给予设计的整合素α(v)β(3)和α(v)β(5)适配体配体后，诱导产生的共价多克隆抗体与适配体配体自组装，动物对植入的肿瘤产生即时的、化学编程的多克隆反应。在不借助辅助治疗的情况下观察到了显著的治疗反应。化学编程的免疫反应由抗体依赖性细胞毒性和补体介导的细胞毒性驱动。我们认为，这种化学驱动的疫苗学方法尚未得到充分探索，可能为预防那些已证明对生物学驱动的疫苗方法难以攻克的疾病的疫苗提供途径。
