Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
Division of Comparative Medicine, Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Sci Adv. 2020 Feb 5;6(6):eaay9258. doi: 10.1126/sciadv.aay9258. eCollection 2020 Feb.
Pertussis continues to cause considerable infant mortality world-wide, which could be addressed in part by passive immunization strategies. Antibody hu1B7 is a candidate therapeutic that potently neutralizes pertussis toxin in vitro, prevents leukocytosis in mice and treats established disease in weanling baboons as part of an antibody cocktail. Here, we evaluated the potential for hu1B7 and an extended half-life hu1B7 variant to prevent death, leukocytosis and other clinical symptoms in a newborn baboon model that mimics many aspects of human disease. We administered a single antibody dose to newborn baboons five weeks prior to experimental infection. While all animals were heavily colonized with , prophylaxed animals showed significantly greater survival ( < 0.005), delayed and suppressed leukocytosis ( < 0.01) and enhanced clinical outcomes, including coughing ( < 0.01), as compared to controls. Together, this work demonstrates that a single neutralizing anti-PTx antibody is sufficient to prevent clinical pertussis symptoms.
百日咳仍然在全球范围内导致相当大的婴儿死亡率,这在一定程度上可以通过被动免疫策略来解决。抗体 hu1B7 是一种候选治疗药物,它在体外能有效中和百日咳毒素,预防小鼠白细胞增多,并在断奶狨猴中治疗已建立的疾病,作为抗体鸡尾酒的一部分。在这里,我们评估了 hu1B7 和一种延长半衰期的 hu1B7 变体在模拟人类疾病许多方面的新生狨猴模型中预防死亡、白细胞增多和其他临床症状的潜力。我们在实验感染前五周给新生狨猴单次抗体剂量。虽然所有动物都被 严重定植,但预防性治疗的动物的存活率显著更高(<0.005),白细胞增多延迟且受到抑制(<0.01),临床结果得到改善,包括咳嗽(<0.01),与对照组相比。总之,这项工作表明,单次中和抗-PTx 抗体足以预防临床百日咳症状。