Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
Vaccine. 2010 Apr 19;28(18):3231-7. doi: 10.1016/j.vaccine.2010.02.014. Epub 2010 Feb 24.
Induction of immunity at mucosal surfaces is thought to be an essential feature in the protection of the host against the many pathogens that gain access through these surfaces. Here we describe how strong local and systemic immune responses can be generated when proteins are genetically conjugated to pneumolysin (PLY) from Streptococcus pneumoniae. Using green fluorescent protein (eGFP) and PsaA from S. pneumoniae, we have shown that genetic fusion (eGFPPLY and PsaAPLY) is essential to ensure high levels of antigen specific IgG and IgA in the serum and at mucosal surfaces. This form of vaccination is highly effective with antigen specific antibodies detected after a single dose of nanogram quantities of the conjugated proteins. In addition, generation of a non-toxic variant (eGFPDelta6PLY) indicated that while the toxic activity of PLY was not essential for adjuvanticity, it contributed to the magnitude of the response generated. Whilst vaccination with the PsaAPLY fusion proteins did not protect the animals from challenge, these studies confirm the utility of pneumolysin to act as a novel mucosal adjuvant to substantially increase the local and systemic humoral response to genetically fused protein antigens.
在黏膜表面诱导免疫被认为是宿主抵御通过这些表面进入的许多病原体的重要特征。在这里，我们描述了当蛋白质与肺炎链球菌（Streptococcus pneumoniae）的肺炎球菌溶血素（pneumolysin，PLY）发生基因融合时，如何产生强烈的局部和全身免疫反应。我们使用绿色荧光蛋白（green fluorescent protein，eGFP）和肺炎球菌表面黏附素 A（Pneumococcal surface adhesin A，PsaA），表明基因融合（eGFPPLY 和 PsaAPLY）对于确保血清和黏膜表面的抗原特异性 IgG 和 IgA 达到高水平是至关重要的。这种疫苗接种形式非常有效，单次接种纳克数量的缀合蛋白后即可检测到抗原特异性抗体。此外，非毒性变异体（eGFPDelta6PLY）的产生表明，尽管 PLY 的毒性活性对于佐剂作用不是必需的，但它有助于产生的反应幅度。虽然用 PsaAPLY 融合蛋白进行疫苗接种不能保护动物免受挑战，但这些研究证实了肺炎球菌溶血素作为一种新型黏膜佐剂的效用，可以大大增强对基因融合蛋白抗原的局部和全身体液免疫反应。
