Price Nancy L, Goyette-Desjardins Guillaume, Nothaft Harald, Valguarnera Ezequiel, Szymanski Christine M, Segura Mariela, Feldman Mario F
Department of Biological Sciences, University of Alberta Edmonton, Alberta T6G 2E9 Canada.
Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal Saint-Hyacinthe, Quebec, J2S 2M2 Canada.
Sci Rep. 2016 Apr 22;6:24931. doi: 10.1038/srep24931.
The World Health Organization has indicated that we are entering into a post-antibiotic era in which infections that were routinely and successfully treated with antibiotics can now be lethal due to the global dissemination of multidrug resistant strains. Conjugate vaccines are an effective way to create a long-lasting immune response against bacteria. However, these vaccines present many drawbacks such as slow development, high price, and batch-to-batch inconsistencies. Alternate approaches for vaccine development are urgently needed. Here we present a new vaccine consisting of glycoengineered outer membrane vesicles (geOMVs). This platform exploits the fact that the initial steps in the biosynthesis of most bacterial glycans are similar. Therefore, it is possible to easily engineer non-pathogenic Escherichia coli lab strains to produce geOMVs displaying the glycan of the pathogen of interest. In this work we demonstrate the versatility of this platform by showing the efficacy of geOMVs as vaccines against Streptococcus pneumoniae in mice, and against Campylobacter jejuni in chicken. This cost-effective platform could be employed to generate vaccines to prevent infections caused by a wide variety of microbial agents in human and animals.
世界卫生组织指出，我们正在进入一个后抗生素时代，在这个时代，过去常规使用抗生素就能成功治疗的感染，如今由于多重耐药菌株的全球传播，可能会致命。结合疫苗是产生针对细菌的持久免疫反应的有效方法。然而，这些疫苗存在许多缺点，如研发缓慢、价格高昂以及批次间不一致。迫切需要开发疫苗的替代方法。在此，我们展示了一种由糖工程化外膜囊泡（geOMV）组成的新型疫苗。该平台利用了大多数细菌聚糖生物合成的初始步骤相似这一事实。因此，能够轻松改造非致病性大肠杆菌实验室菌株，以产生展示感兴趣病原体聚糖的geOMV。在这项研究中，我们通过展示geOMV作为小鼠抗肺炎链球菌疫苗以及鸡抗空肠弯曲菌疫苗的有效性，证明了该平台的多功能性。这个具有成本效益的平台可用于生产疫苗，以预防人类和动物中由多种微生物病原体引起的感染。
