Locht Camille, Papin James F, Lecher Sophie, Debrie Anne-Sophie, Thalen Marcel, Solovay Ken, Rubin Keith, Mielcarek Nathalie
Institut Pasteur de Lille, Center for Infection and Immunity of Lille.
University of Lille.
J Infect Dis. 2017 Jul 1;216(1):117-124. doi: 10.1093/infdis/jix254.
Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal colonization by Bordetella pertussis, the principal causative agent of whooping cough. Here, we used a baboon model to test the protective potential of the novel, live attenuated pertussis vaccine candidate BPZE1. A single intranasal/intratracheal inoculation of juvenile baboons with BPZE1 resulted in transient nasopharyngeal colonization and induction of immunoglobulin G and immunoglobulin A to all antigens tested, while causing no adverse symptoms or leukocytosis. When BPZE1-vaccinated baboons were challenged with a high dose of a highly virulent B. pertussis isolate, they were fully protected against disease, whereas naive baboons developed illness (with 1 death) and leukocytosis. Total postchallenge nasopharyngeal virulent bacterial burden of vaccinated animals was substantially reduced (0.002%) compared to naive controls, providing promising evidence in nonhuman primates that BPZE1 protects against both pertussis disease and B. pertussis infection.
有证据表明,许多工业化国家百日咳疫情的死灰复燃可能是由于目前的疫苗未能预防百日咳的主要病原体百日咳博德特氏菌在鼻咽部的定植。在此,我们使用狒狒模型来测试新型减毒活百日咳疫苗候选株BPZE1的保护潜力。用BPZE1对幼年狒狒进行单次鼻内/气管内接种,导致短暂的鼻咽部定植,并诱导产生针对所有测试抗原的免疫球蛋白G和免疫球蛋白A,同时未引起任何不良症状或白细胞增多。当用高剂量的高毒力百日咳博德特氏菌分离株对接种BPZE1的狒狒进行攻击时,它们完全受到保护不发病,而未接种的狒狒则发病(1只死亡)并出现白细胞增多。与未接种的对照组相比,接种动物攻击后鼻咽部有毒力细菌的总负担大幅降低(0.002%),这在非人灵长类动物中提供了有前景的证据,表明BPZE1可预防百日咳疾病和百日咳博德特氏菌感染。