Champion Olivia L, Gourlay Louise J, Scott Andrew E, Lassaux Patricia, Conejero Laura, Perletti Lucia, Hemsley Claudia, Prior Joann, Bancroft Gregory, Bolognesi Martino, Titball Richard W
College of Life and Environmental Sciences, University of Exeter, Exeter, UK.
Department of Biosciences, University of Milan, Milan 20133, Italy.
Vaccine. 2016 Mar 29;34(14):1665-71. doi: 10.1016/j.vaccine.2016.02.038. Epub 2016 Feb 23.
There is an urgent need for an effective vaccine against human disease caused by Burkholderia pseudomallei, and although a wide range of candidates have been tested in mice none provide high level protection. We considered this might reflect the inability of these vaccine candidates to protect against chronic disease. Using Q-RT PCR we have identified 6 genes which are expressed in bacteria colonising spleens and lungs of chronically infected mice. Three of the genes (BPSL1897, BPSL3369 and BPSL2287) have been expressed in Escherichia coli and the encoded proteins purified. We have also included BPSL2765, a protein known to induce immune responses associated with a reduced incidence of chronic/recurrent disease in humans. Immunisation of mice with a combination of these antigens resulted in the induction of antibody responses against all of the proteins. Compared with mice immunised with capsular polysaccharide or LolC protein, mice immunised with the combination of chronic stage antigens showed enhanced protection against experimental disease in mice.
迫切需要一种针对由伯克霍尔德菌引起的人类疾病的有效疫苗，尽管已经在小鼠中测试了多种候选疫苗，但没有一种能提供高水平的保护。我们认为这可能反映出这些候选疫苗无法预防慢性病。使用定量逆转录聚合酶链反应（Q-RT PCR），我们鉴定出了6个在慢性感染小鼠脾脏和肺部定殖的细菌中表达的基因。其中3个基因（BPSL1897、BPSL3369和BPSL2287）已在大肠杆菌中表达，并对编码的蛋白质进行了纯化。我们还纳入了BPSL2765，一种已知能诱导与人类慢性/复发性疾病发病率降低相关的免疫反应的蛋白质。用这些抗原的组合对小鼠进行免疫，可诱导针对所有蛋白质的抗体反应。与用荚膜多糖或LolC蛋白免疫的小鼠相比，用慢性期抗原组合免疫的小鼠对实验性疾病的保护作用增强。
