Use of Recombinant Virus Replicon Particles for Vaccination against Mycobacterium ulcerans Disease.
Use of Recombinant Virus Replicon Particles for Vaccination against Mycobacterium ulcerans Disease.
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DOI：
10.1371/journal.pntd.0004011
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发表时间：
2015
影响因子：
3.8
通讯作者：
Pluschke G
中科院分区：
文献类型：
--
作者：
Bolz M;Kerber S;Zimmer G;Pluschke G
由溃疡分枝杆菌感染引起的布鲁里溃疡是一种皮肤和皮下组织坏死性疾病，在西非国家的农村地区最为流行。大多数患者的临床表现是四肢溃疡，可以通过8周的抗生素治疗来治疗。然而，瘢痕和永久性残疾经常发生，布鲁里溃疡仍然导致高发病率。迄今为止，还没有针对这种疾病的疫苗，但如果用于预防和治疗，将有很大的好处。在本研究中，水泡性口炎病毒为基础的RNA复制子颗粒编码的M。产生溃疡蛋白MUL 2232和MUL 3720，并在体外表征重组抗原的表达。用重组复制子颗粒免疫小鼠，诱导出与M.溃疡细胞使用MUL 2232-重组复制子颗粒和重组MUL 2232蛋白的初免-加强免疫方案在M.溃疡感染。我们得出结论，基于MUL 2232抗原的单价疫苗可能无法充分控制M。人类的溃疡感染。溃疡分枝杆菌感染可导致皮肤和底层软组织的缓慢进展的溃疡性疾病，称为布鲁里溃疡。这种疾病在非洲农村社区最为普遍，获得保健设施的机会有限。预防这种疾病的最有效手段是迄今为止还没有针对布鲁里溃疡的疫苗。在本研究中，我们研究了表达两个M.溃疡抗原MUL 2232和MUL 3720。用这些水泡性口炎病毒复制子颗粒免疫小鼠导致在免疫动物中诱导体液免疫应答以及细胞免疫应答。随后在M.溃疡感染表明，采用MUL 2232初免-加强方法免疫的小鼠中细菌负荷仅有限减少。最有可能的是，仅具有一种抗原的疫苗制剂将不能提供针对人类布鲁里溃疡的保护。
Buruli ulcer, caused by infection with Mycobacterium ulcerans, is a necrotizing disease of the skin and subcutaneous tissue, which is most prevalent in rural regions of West African countries. The majority of clinical presentations seen in patients are ulcers on limbs that can be treated by eight weeks of antibiotic therapy. Nevertheless, scarring and permanent disabilities occur frequently and Buruli ulcer still causes high morbidity. A vaccine against the disease is so far not available but would be of great benefit if used for prophylaxis as well as therapy. In the present study, vesicular stomatitis virus-based RNA replicon particles encoding the M. ulcerans proteins MUL2232 and MUL3720 were generated and the expression of the recombinant antigens characterized in vitro. Immunisation of mice with the recombinant replicon particles elicited antibodies that reacted with the endogenous antigens of M. ulcerans cells. A prime-boost immunization regimen with MUL2232-recombinant replicon particles and recombinant MUL2232 protein induced a strong immune response but only slightly reduced bacterial multiplication in a mouse model of M. ulcerans infection. We conclude that a monovalent vaccine based on the MUL2232 antigen will probably not sufficiently control M. ulcerans infection in humans. Infection with Mycobacterium ulcerans can lead to a slow progressing, ulcerative disease of the skin and underlying soft tissue called Buruli ulcer. The disease is most prevalent in rural African communities with limited access to health care facilities. The most efficient means to prevent the disease, a vaccine against Buruli ulcer is not available to date. In the present study we investigated the immunogenicity and protective potential of a single cycle virus system expressing the two M. ulcerans antigens MUL2232 and MUL3720. Immunization of mice with those vesicular stomatitis virus replicon particles led to the induction of humoral as well as cellular immune responses in the immunized animals. Subsequent challenge experiments in a mouse model of M. ulcerans infection demonstrated only a limited reduction of bacterial burden in mice immunized with a prime-boost approach with MUL2232. Most probably, a vaccine formulation with only one antigen will not be able to provide protection against Buruli ulcer in humans.