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编码肺炎克雷伯菌外膜蛋白A和OmpK36的DNA疫苗对小鼠的保护效力

Protective efficacy of DNA vaccines encoding outer membrane protein A and OmpK36 of Klebsiella pneumoniae in mice.

作者信息

Kurupati Prathiba, Ramachandran N P, Poh Chit Laa

机构信息

Department of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.

出版信息

Clin Vaccine Immunol. 2011 Jan;18(1):82-8. doi: 10.1128/CVI.00275-10. Epub 2010 Nov 3.

Abstract

The immunogenicity of DNA vaccines expressing outer membrane proteins as antigens was evaluated in this study. DNA vaccines consisting of vector pVAX1 expressing either outer membrane protein A or OmpK36 were injected into mice by either the intradermal or the intramuscular route. Antibodies elicited were shown to be specifically reactive to OmpA and OmpK36 by immunoblotting. The immunoglobulin G (IgG) antibodies elicited by both vaccines included IgG1, IgG2a, IgG2b, and IgG3. Immunized mice exhibited a predominance of IgG1 over IgG2a, therefore indicating a stronger humoral response. Mice receiving either of the DNA vaccines produced high levels of interleukin-12 (IL-12) and IL-10 and low levels of gamma interferon, suggesting the induction of a mixed Th1 and Th2 response. Sera from DNA vaccine-immunized mice had significantly higher opsonic activity in opsonophagocytic assays than did sera from the control mice. The level of protection afforded by pOmpK36 DNA injected intradermally into mice was the highest. These results suggest that both OmpA and OmpK36 are excellent candidates for use in future studies of vaccination against infections caused by Klebsiella pneumoniae. This is the first study which established the efficacy of protection afforded by DNA vaccines based on outer membrane proteins against K. pneumoniae infections.

摘要

本研究评估了表达外膜蛋白作为抗原的DNA疫苗的免疫原性。将由表达外膜蛋白A或OmpK36的载体pVAX1组成的DNA疫苗通过皮内或肌肉注射途径注入小鼠体内。通过免疫印迹法显示,所诱导的抗体对OmpA和OmpK36具有特异性反应。两种疫苗诱导产生的免疫球蛋白G(IgG)抗体包括IgG1、IgG2a、IgG2b和IgG3。免疫小鼠体内IgG1的含量高于IgG2a,因此表明其体液免疫反应更强。接受任何一种DNA疫苗的小鼠均产生高水平的白细胞介素-12(IL-12)和IL-10以及低水平的γ干扰素,提示诱导了混合的Th1和Th2反应。在调理吞噬试验中,DNA疫苗免疫小鼠的血清调理活性显著高于对照小鼠血清。皮内注射pOmpK36 DNA给予小鼠的保护水平最高。这些结果表明,OmpA和OmpK36都是未来用于肺炎克雷伯菌感染疫苗接种研究的优秀候选抗原。这是第一项证实基于外膜蛋白的DNA疫苗对肺炎克雷伯菌感染具有保护效力的研究。

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