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经粘膜给予表达包膜结构域III抗原的重组乳酸乳球菌菌株后诱导出针对2型登革病毒的中和抗体。

Induction of neutralizing antibodies against dengue virus type 2 upon mucosal administration of a recombinant Lactococcus lactis strain expressing envelope domain III antigen.

作者信息

Sim Adrian C N, Lin Wenwei, Tan Grace K X, Sim Magenta S T, Chow Vincent T K, Alonso Sylvie

机构信息

Immunology Programme, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

出版信息

Vaccine. 2008 Feb 26;26(9):1145-54. doi: 10.1016/j.vaccine.2007.12.047. Epub 2008 Jan 18.

Abstract

Mucosal vaccines present several advantages over conventional parenteral vaccines including their ease of administration and low cost, both criteria being priorities for developing countries plagued by infectious diseases. A recombinant Lactococcus lactis strain producing the envelope domain III (EDIII) antigen from dengue virus serotype 2 was engineered, and the ability of the live recombinant bacteria to trigger a systemic anti-EDIII IgG antibody response upon nasal or oral administration to BALB/c and C57BL/6 mice was investigated. Results showed that the antibody response depended on the route of administration and on the mouse strain inoculated. Out of six, two and three C57BL/6 mice orally and nasally inoculated with the recombinant bacteria, respectively, displayed anti-EDIII antibody responses higher than that obtained in the mouse group intraperitoneally (i.p.) immunized with heat-inactivated dengue 2 virus. The protective potential of the immune sera was measured using the plaque reduction neutralizing test (PRNT) and results indicated that high anti-EDIII antibody levels did not correlate directly with high neutralizing activities. Immune sera from orally inoculated mice were found the most potent to neutralize in vitro dengue infection with neutralizing antibody activities in some cases higher than that obtained with the immune sera from mice i.p. injected with heat-inactivated virus.

摘要

黏膜疫苗与传统的肠胃外疫苗相比具有若干优势,包括易于接种且成本低,这两个标准都是受传染病困扰的发展中国家的优先事项。构建了一种重组乳酸乳球菌菌株,该菌株可产生来自登革病毒2型的包膜结构域III(EDIII)抗原,并研究了活重组细菌经鼻内或口服给予BALB/c和C57BL/6小鼠后引发全身性抗EDIII IgG抗体反应的能力。结果表明,抗体反应取决于给药途径和接种的小鼠品系。在分别经口和鼻内接种重组细菌的六只C57BL/6小鼠中,有两只和三只显示出的抗EDIII抗体反应高于腹腔内(i.p.)接种热灭活登革2型病毒的小鼠组。使用蚀斑减少中和试验(PRNT)测量免疫血清的保护潜力,结果表明高抗EDIII抗体水平与高中和活性没有直接相关性。发现经口接种小鼠的免疫血清在体外中和登革热感染方面最有效,在某些情况下其中和抗体活性高于腹腔内注射热灭活病毒的小鼠的免疫血清。

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