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生淀粉微球作为卡介苗佐剂:其效力取决于感染菌株的毒力。

Raw starch microparticles as BCG adjuvant: Their efficacy depends on the virulence of the infection strains.

机构信息

CONACYT, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), A.P. 70228, Ciudad Universitaria, Ciudad de México 04510, Mexico; Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), A.P. 70228, Ciudad Universitaria, Ciudad de México 04510, Mexico.

Posgrado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM), A.P. 70228, Ciudad Universitaria, Ciudad de México 04510, Mexico.

出版信息

Vaccine. 2019 Sep 10;37(38):5731-5737. doi: 10.1016/j.vaccine.2019.04.027. Epub 2019 Apr 15.

Abstract

The persistence of tuberculosis (TB) as one of the top 10 causes of death worldwide, the growing incidence of multidrug-resistant tuberculosis and the controversial efficacy of the Bacille Calmette-Guérin (BCG) vaccine drives the development of new generation multistage vaccines against this disease that can boost BCG-primed immunity. The use of polymeric microparticles for this purpose increases due to their advantages, especially their good safety levels and intrinsic immunostimulant properties. We recently explored and demonstrated the reinforcing and adjuvant potential of starch microparticles (SMPs) that administered intranasally to BCG-primed BALB/c mice, alone or in combination with a recombinant antigen, increased survival rates and induced a reduction of bacterial load in the lungs of mice infected with tuberculosis. Here, we tested the effect of SMPs added to the BCG vaccine as adjuvant to the whole-cell vaccine and investigated their contribution to the improvement of the protective efficacy of subcutaneous vaccination in mice challenged with virulent strains of Mycobacterium tuberculosis. As expected, our results were dependent on the infection strains, showing that virulence is a crucial factor that affects the adjuvant activity of SMPs. Our results also confirm the adjuvant activity of this carbohydrate and its usefulness in diverse vaccination strategies not only for mucosal but also for parenteral administration.

摘要

结核病(TB)作为全球十大死因之一持续存在,耐多药结核病的发病率不断上升,卡介苗(BCG)疫苗的疗效存在争议,这促使人们开发针对这种疾病的新一代多阶段疫苗,以增强 BCG 引发的免疫。由于其优势,特别是良好的安全性水平和固有免疫刺激特性,人们越来越多地使用聚合物微球来实现这一目的。我们最近探索并证明了淀粉微球(SMP)的增强和佐剂潜力,将其鼻内给予 BCG 初免的 BALB/c 小鼠,单独或与重组抗原联合使用,可提高存活率并降低感染结核分枝杆菌的小鼠肺部的细菌负荷。在这里,我们测试了将 SMP 添加到 BCG 疫苗中作为全细胞疫苗佐剂的效果,并研究了它们对皮下接种疫苗在受到结核分枝杆菌强毒株挑战的小鼠中提高保护效力的贡献。正如预期的那样,我们的结果取决于感染株,表明毒力是影响 SMP 佐剂活性的关键因素。我们的结果还证实了这种碳水化合物的佐剂活性及其在不同疫苗接种策略中的有用性,不仅适用于粘膜途径,也适用于肠胃外途径。

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