Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Clin Exp Immunol. 2019 May;196(2):178-188. doi: 10.1111/cei.13286. Epub 2019 Apr 8.
Burkholderia pseudomallei is the causative agent of melioidosis. Historically believed to be a relatively rare human disease in tropical countries, a recent study estimated that, worldwide, there are approximately 165 000 human melioidosis cases per year, more than half of whom die. The bacterium is inherently resistant to many antibiotics and treatment of the disease is often protracted and ineffective. There is no licensed vaccine against melioidosis, but a vaccine is predicted to be of value if used in high-risk populations. There has been progress over the last decade in the pursuit of an effective vaccine against melioidosis. Animal models of disease including mouse and non-human primates have been developed, and these models show that antibody responses play a key role in protection against melioidosis. Surprisingly, although B. pseudomallei is an intracellular pathogen there is limited evidence that CD8 T cells play a role in protection. It is evident that a multi-component vaccine, incorporating one or more protective antigens, will probably be essential for protection because of the pathogen's sophisticated virulence mechanisms as well as strain heterogeneity. Multi-component vaccines in development include glycoconjugates, multivalent subunit preparations, outer membrane vesicles and other nano/microparticle platforms and live-attenuated or inactivated bacteria. A consistent finding with vaccine candidates tested in mice is the ability to induce sterilizing immunity at low challenge doses and extended time to death at higher challenge doses. Further research to identify ways of eliciting more potent immune responses might provide a path for licensing an effective vaccine.
类鼻疽伯克霍尔德菌是类鼻疽病的病原体。历史上，人们认为这种细菌在热带国家是一种相对罕见的人类疾病，但最近的一项研究估计，在全球范围内，每年约有 165000 例人类类鼻疽病病例，其中超过一半的人死亡。这种细菌天生对许多抗生素具有耐药性，而且疾病的治疗往往漫长而无效。目前还没有针对类鼻疽病的许可疫苗，但如果在高危人群中使用，预测疫苗将具有价值。在过去的十年中，人们在寻求有效的类鼻疽病疫苗方面取得了进展。已经开发出包括小鼠和非人类灵长类动物在内的疾病动物模型，这些模型表明抗体反应在预防类鼻疽病方面起着关键作用。令人惊讶的是，尽管类鼻疽伯克霍尔德菌是一种细胞内病原体，但有有限的证据表明 CD8+T 细胞在保护中发挥作用。显然，由于病原体复杂的毒力机制和菌株异质性，包含一种或多种保护性抗原的多组分疫苗可能是预防疾病所必需的。正在开发的多组分疫苗包括糖缀合物、多价亚单位制剂、外膜囊泡和其他纳米/微粒平台以及减毒或灭活细菌。在小鼠中测试的候选疫苗的一个一致发现是，它们能够在低挑战剂量下诱导绝育性免疫，并在高挑战剂量下延长死亡时间。进一步研究以确定引发更有效的免疫反应的方法可能为许可有效的疫苗提供一条途径。
