Seixas António M M, Sousa Sílvia A, Leitão Jorge H
Department of Bioengineering, IBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Associate Laboratory, i4HB-Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Vaccines (Basel). 2022 Oct 25;10(11):1789. doi: 10.3390/vaccines10111789.
The discovery of antimicrobials is an outstanding achievement of mankind that led to the development of modern medicine. However, increasing antimicrobial resistance observed worldwide is rendering commercially available antimicrobials ineffective. This problem results from the bacterial ability to adapt to selective pressure, leading to the development or acquisition of multiple types of resistance mechanisms that can severely affect the efficacy of antimicrobials. The misuse, over-prescription, and poor treatment adherence by patients are factors strongly aggravating this issue, with an epidemic of infections untreatable by first-line therapies occurring over decades. Alternatives are required to tackle this problem, and immunotherapies are emerging as pathogen-specific and nonresistance-generating alternatives to antimicrobials. In this work, four types of antibody formats and their potential for the development of antibody-based immunotherapies against bacteria are discussed. These antibody isotypes include conventional mammalian polyclonal antibodies that are used for the neutralization of toxins; conventional mammalian monoclonal antibodies that currently have 100 IgG mAbs approved for therapeutic use; immunoglobulin Y found in birds and an excellent source of high-quality polyclonal antibodies able to be purified noninvasively from egg yolks; and single domain antibodies (also known as nanobodies), a recently discovered antibody format (found in camelids and nurse sharks) that allows for a low-cost synthesis in microbial systems, access to hidden or hard-to-reach epitopes, and exhibits a high modularity for the development of complex structures.
抗菌药物的发现是人类的一项杰出成就，它推动了现代医学的发展。然而，全球范围内日益增加的抗菌药物耐药性正使市售抗菌药物失效。这个问题源于细菌适应选择性压力的能力，导致多种耐药机制的产生或获得，这会严重影响抗菌药物的疗效。患者的滥用、过度处方和治疗依从性差是严重加剧这一问题的因素，数十年来一直存在一线治疗无法治愈的感染流行情况。需要有替代方法来解决这个问题，免疫疗法正在作为针对病原体的、不会产生耐药性的抗菌药物替代方法而兴起。在这项工作中，讨论了四种抗体形式及其用于开发基于抗体的抗细菌免疫疗法的潜力。这些抗体亚型包括用于中和毒素的传统哺乳动物多克隆抗体；目前有100种IgG单克隆抗体被批准用于治疗的传统哺乳动物单克隆抗体；鸟类体内发现的免疫球蛋白Y，它是能够从蛋黄中无创纯化的优质多克隆抗体的极佳来源；以及单域抗体（也称为纳米抗体），这是一种最近发现的抗体形式（在骆驼科动物和护士鲨中发现），它能够在微生物系统中低成本合成，能够识别隐藏或难以触及的表位，并且在开发复杂结构方面具有高度的模块化。
