Cherwonogrodzky John W, Barabé Nicole D, Grigat Michelle L, Lee William E, Poirier Robert T, Jager Scott J, Berger Bradley J
Defence Research and Development Canada (DRDC), Suffield Research Centre, Medicine Hat, Alberta, Canada
Defence Research and Development Canada (DRDC), Suffield Research Centre, Medicine Hat, Alberta, Canada.
Clin Vaccine Immunol. 2014 Dec;21(12):1681-8. doi: 10.1128/CVI.00447-14. Epub 2014 Oct 15.
A subunit vaccine candidate was produced from Brucella suis 145 (biovar 4; expressing both the A antigen of Brucella abortus and the M antigen of Brucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of three Brucella species most pathogenic for humans, i.e., B. abortus, B. melitensis, and B. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice against B. suis 145 infection (5 × 10(5) CFU), and a single injection of 1 μg of this subunit vaccine protected mice from B. suis 145 challenge for at least 14 months. A single immunization induced a serum IgG response to Brucella antigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains of Brucella and represents a promising candidate for further evaluation.
一种候选亚单位疫苗是由猪布鲁氏菌145(生物变种4;表达流产布鲁氏菌的A抗原和羊布鲁氏菌的M抗原)制备而成。该制剂主要由多糖(PS;>90%[重量/重量];细胞相关PS和胞外PS合并)和少量蛋白质(1%至3%)组成,无明显核酸。用对人类致病性最强的三种布鲁氏菌的代表性菌株,即流产布鲁氏菌、羊布鲁氏菌和猪布鲁氏菌攻击接种疫苗的小鼠时,这些小鼠受到了保护(与未接种疫苗的对照相比,其细菌定植有统计学显著减少)。仅1纳克该疫苗(无添加佐剂)就能保护小鼠免受猪布鲁氏菌145感染(5×10⁵CFU),单次注射1微克这种亚单位疫苗能使小鼠在至少14个月内免受猪布鲁氏菌145攻击。单次免疫诱导了对布鲁氏菌抗原的血清IgG反应,该反应可持续升高长达9周。在疫苗制备过程中使用加热(即沸水浴、高压灭菌)表明其具有热稳定性。该方法还确保了安全性。所生产的疫苗具有免疫原性,对多种布鲁氏菌菌株具有高度保护作用,是进一步评估的有前景的候选疫苗。