Nyazema Kudzai B, Shey Bong-Akee, Sei Clara J, Peters Remco P H, Maningi Nontuthuko E, Fischer Gerald W, Bernard Fourie P
Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, South Africa.
Vaccine and Antibody Development, Longhorn Vaccines and Diagnostics, Gaithersburg, MD, USA.
J Clin Tuberc Other Mycobact Dis. 2024 Apr 1;35:100435. doi: 10.1016/j.jctube.2024.100435. eCollection 2024 May.
Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 µg/mL to live cultures of , , , , and American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multi-drug resistant, and extensively drug resistant strains using indirect enzyme-linked immunosorbent assays. These three MAB concentrations were selected from a range of concentrations used in previous optimization (binding and functional) assays. Both MABs bound to all mycobacterial species and sub-types tested, albeit to varying degrees. Statistically significant differences in MAB binding activity were observed when comparing the highest and lowest MAB concentrations (p < 0.05) for both MABs GG9 and JG7, irrespective of the resistance profile. Binding affinity increased with an increase in MAB concentration, and optimal binding was observed at 25 µg/mL. JG7 showed better binding activity than GG9. Both MABs also bound to five MOTT species, albeit at varied levels. This non-selective binding to different mycobacterial species suggests a potential role for GG9 and JG7 as adjunctive agents in anti-TB chemotherapy with the aim to enhance bacterial killing.
除了结核病（TB）治疗中的其他挑战外，抗菌药物耐药性引发了人们对宿主导向干预措施的新兴趣，包括抗体作为辅助治疗药物的作用。本研究使用间接酶联免疫吸附测定法，评估了两种新型IgG1调理单克隆抗体（MABs；GG9和JG7）在5、10和25μg/mL浓度下对美国典型培养物保藏中心的、、、和实验室参考菌株以及临床敏感、耐多药和广泛耐药菌株活培养物的结合效力。这三种MAB浓度是从先前优化（结合和功能）试验中使用的一系列浓度中选择的。两种MABs均与所有测试的分枝杆菌种类和亚型结合，尽管程度不同。在比较GG9和JG7两种MABs的最高和最低MAB浓度时，观察到MAB结合活性存在统计学显著差异（p<0.05），无论其耐药情况如何。结合亲和力随MAB浓度的增加而增加，在25μg/mL时观察到最佳结合。JG7显示出比GG9更好的结合活性。两种MABs也与五种非结核分枝杆菌结合，尽管结合水平不同。这种对不同分枝杆菌种类的非选择性结合表明GG9和JG7作为抗结核化疗辅助药物具有潜在作用，旨在增强细菌杀伤作用。
