Broos Katleen, Janssens Michiel E, De Goeyse Ine, Vanlandschoot Peter, Leroux-Roels Geert, Geysen Dirk, Guisez Yves
Laboratory of Plant Physiology, Department of Biology, University of Antwerp, Antwerp, Belgium.
Clin Vaccine Immunol. 2008 May;15(5):852-8. doi: 10.1128/CVI.00382-07. Epub 2008 Mar 26.
The hepatitis B virus core (HBc) virus-like particle (VLP) is known as one of the most immunogenic antigens and carrier vehicles in different immunization strategies. Recent findings are suggesting the potential of the HBc VLPs as an oral immunogen. Here, we focus on the induction of serum humoral responses by oral administration of HBc VLPs in preparations substantially free of lipopolysaccharide and immunomodulating encapsidated RNA. The full-length HBc antigen was used, because the C-terminal arginine-rich tail may contribute to the immunogenicity of the antigen as the region is involved in cell surface heparan sulfate binding and internalization of the protein. Serum antibody levels and isotypes were determined following oral administration of the HBc VLPs with the perspective of using the HBc VLP as an immunostimulatory and carrier molecule for epitopes of blood-borne diseases in oral immunization vaccination strategies. Following oral administration of the HBc VLP preparations to mice, a strong serum humoral response was induced with mainly immunoglobulin G2a (IgG2a) antibodies, pointing toward a Th1 response which is essential in the control of intracellular pathogens. Intraperitoneal immunization with the HBc VLP induced a stronger, mixed Th1/Th2 response. Finally, a comparison was made with the induced serum humoral response following oral administration of the recombinant cholera toxin B pentamer, a commonly used oral immunogen. These immunizations, in contrast, induced predominantly antibodies of the IgG1 isotype, indicative of a Th2 response. These data suggest that the HBc VLP can be an interesting carrier molecule in oral vaccine development.
乙肝病毒核心(HBc)病毒样颗粒(VLP)是不同免疫策略中最具免疫原性的抗原和载体之一。最近的研究结果表明HBc VLP作为口服免疫原具有潜力。在此,我们聚焦于在基本不含脂多糖和免疫调节性衣壳化RNA的制剂中口服HBc VLP诱导血清体液免疫反应。使用全长HBc抗原,因为富含精氨酸的C末端尾巴可能有助于抗原的免疫原性,该区域参与细胞表面硫酸乙酰肝素结合和蛋白质的内化。从将HBc VLP用作口服免疫接种策略中血源性病原体表位的免疫刺激和载体分子的角度出发,在口服HBc VLP后测定血清抗体水平和亚型。将HBc VLP制剂口服给予小鼠后,诱导出强烈的血清体液免疫反应,主要产生免疫球蛋白G2a(IgG2a)抗体,表明是Th1反应,这在控制细胞内病原体中至关重要。用HBc VLP进行腹腔免疫诱导出更强的、混合的Th1/Th2反应。最后,与口服常用的重组霍乱毒素B五聚体后诱导的血清体液免疫反应进行了比较。相比之下,这些免疫主要诱导出IgG1亚型抗体,表明是Th2反应。这些数据表明HBc VLP在口服疫苗开发中可能是一种有趣的载体分子。