Casey William T, Spink Natasha, Cia Felipe, Collins Cassandra, Romano Maria, Berisio Rita, Bancroft Gregory J, McClean Siobhán
Centre of Microbial Host Interactions, ITT Dublin, Tallaght, Dublin 24, Ireland.
Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
Vaccine. 2016 May 17;34(23):2616-21. doi: 10.1016/j.vaccine.2016.03.088. Epub 2016 Apr 16.
Burkholderia pseudomallei is the causative agent of melioidosis, which is associated with a range of clinical manifestations, including sepsis and fatal pneumonia and is endemic in Southeast Asia and Northern Australia. Treatment can be challenging and control of infection involves prolonged antibiotic therapy, yet there are no approved vaccines available to prevent infection. Our aim was to develop and assess the potential of a prophylactic vaccine candidate targeted against melioidosis. The identified candidate is the 22kDa outer membrane protein, OmpW. We previously demonstrated that this protein was immunoprotective in mouse models of Burkholderia cepacia complex (Bcc) infections. We cloned Bp_ompW in Escherichia coli, expressed and purified the protein. Endotoxin free protein administered with SAS adjuvant protected Balb/C mice (75% survival) relative to controls (25% survival) (p<0.05). A potent serological response was observed with IgG2a to IgG1 ratio of 6.0. Furthermore C57BL/6 mice were protected for up to 80 days against a lethal dose of B. pseudomallei and surpassed the efficacy of the live attenuated 2D2 positive control. BpompW is homologous across thirteen sequenced B. pseudomallei strains, indicating that it should be broadly protective against B. pseudomallei. In conclusion, we have demonstrated that BpOmpW is able to induce protective immunity against melioidosis and is likely to be an effective vaccine antigen, possibly in combination with other subunit antigens.
类鼻疽伯克霍尔德菌是类鼻疽的病原体，类鼻疽与一系列临床表现相关，包括败血症和致命性肺炎，在东南亚和澳大利亚北部为地方病。治疗可能具有挑战性，控制感染需要长期抗生素治疗，但目前尚无批准的疫苗可预防感染。我们的目标是开发并评估一种针对类鼻疽的预防性候选疫苗的潜力。鉴定出的候选疫苗是22kDa外膜蛋白OmpW。我们之前证明该蛋白在洋葱伯克霍尔德菌复合体（Bcc）感染的小鼠模型中具有免疫保护作用。我们在大肠杆菌中克隆了Bp_ompW，表达并纯化了该蛋白。与对照组（25%存活）相比，用SAS佐剂给予无内毒素蛋白可保护Balb/C小鼠（75%存活）（p<0.05）。观察到强烈的血清学反应，IgG2a与IgG1的比例为6.0。此外，C57BL/6小鼠在长达80天的时间内受到保护，免受致死剂量的类鼻疽伯克霍尔德菌感染，并且超过了减毒活疫苗2D2阳性对照的效力。BpompW在13株已测序的类鼻疽伯克霍尔德菌菌株中具有同源性，表明它对类鼻疽伯克霍尔德菌应具有广泛的保护作用。总之，我们已经证明BpOmpW能够诱导针对类鼻疽的保护性免疫，并且可能是一种有效的疫苗抗原，可能与其他亚单位抗原联合使用。
