Protective Efficacy of DNA Vaccines Encoding Outer Membrane Protein A and OmpK36 of Klebsiella pneumoniae in Mice
Protective Efficacy of DNA Vaccines Encoding Outer Membrane Protein A and OmpK36 of Klebsiella pneumoniae in Mice
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DOI：
10.1128/cvi.00275-10
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Poh, Chit Laa
中科院分区：
文献类型：
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作者：
Kurupati, Prathiba;Ramachandran, N. P.;Poh, Chit Laa
本研究评价了以外膜蛋白为抗原的DNA疫苗的免疫原性。由表达外膜蛋白A或OmpK36的pVAX1载体组成的DNA疫苗通过皮内或肌内途径注射到小鼠体内。免疫印迹显示，诱导的抗体对OmpA和OmpK36具有特异性反应。两种疫苗诱导的免疫球蛋白G （IgG）抗体包括IgG1、IgG2a、IgG2b和IgG3。免疫小鼠表现出IgG1优于IgG2a，因此表明更强的体液反应。接受任何一种DNA疫苗的小鼠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，表明诱导了混合Th1和Th2反应。DNA疫苗免疫小鼠的血清在调理吞噬实验中比对照小鼠的血清具有明显更高的调理活性。皮下注射pOmpK36 DNA对小鼠的保护水平最高。这些结果表明，OmpA和OmpK36都是未来肺炎克雷伯菌感染疫苗研究的优秀候选者。这是第一个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作用的研究。
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.