Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215.
Microbiol Spectr. 2015 Feb;3(1):AID-0028-2014. doi: 10.1128/microbiolspec.AID-0028-2014.
Despite the availability of antimicrobial drugs, the continued development of microbial resistance--established through escape mutations and the emergence of resistant strains--limits their clinical utility. The discovery of novel, therapeutic, monoclonal antibodies (mAbs) offers viable clinical alternatives in the treatment and prophylaxis of infectious diseases. Human mAb-based therapies are typically nontoxic in patients and demonstrate high specificity for the intended microbial target. This specificity prevents negative impacts on the patient microbiome and avoids driving the resistance of nontarget species. The in vitro selection of human antibody fragment libraries displayed on phage or yeast surfaces represents a group of well-established technologies capable of generating human mAbs. The advantage of these forms of microbial display is the large repertoire of human antibody fragments present during a single selection campaign. Furthermore, the in vitro selection environments of microbial surface display allow for the rapid isolation of antibodies--and their encoding genes--against infectious pathogens and their toxins that are impractical within in vivo systems, such as murine hybridomas. This article focuses on the technologies of phage display and yeast display, as these strategies relate to the discovery of human mAbs for the treatment and vaccine development of infectious diseases.
尽管有抗菌药物可用，但微生物耐药性的持续发展——通过逃逸突变和耐药菌株的出现而确立——限制了它们的临床应用。新型治疗性单克隆抗体 (mAb) 的发现为传染病的治疗和预防提供了可行的临床替代方案。基于人类单克隆抗体的治疗方法在患者中通常无毒，并且对预期的微生物靶标具有高度特异性。这种特异性防止了对患者微生物组的负面影响，并避免了对非目标物种的耐药性驱动。噬菌体或酵母表面展示的人抗体片段文库的体外选择代表了一组成熟的技术，能够产生人 mAb。这些微生物展示形式的优势在于，在单次选择过程中存在大量的人抗体片段。此外，微生物表面展示的体外选择环境允许快速分离针对感染性病原体及其毒素的抗体——及其编码基因——这些在体内系统（如鼠杂交瘤）中是不切实际的。本文重点介绍噬菌体展示和酵母展示技术，因为这些策略与发现用于治疗和疫苗开发传染病的人类单克隆抗体有关。
