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流感病毒囊泡佐以 GPI-0100 佐剂:一种用于节省抗原剂量的强效疫苗制剂。

Influenza virosomes supplemented with GPI-0100 adjuvant: a potent vaccine formulation for antigen dose sparing.

机构信息

Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, P.O.Box 30.001, EB 88, 9700 RB, Groningen, The Netherlands,

出版信息

Med Microbiol Immunol. 2014 Feb;203(1):47-55. doi: 10.1007/s00430-013-0313-2. Epub 2013 Sep 24.

Abstract

Adjuvants can stimulate vaccine-induced immune responses and can contribute decisively to antigen dose sparing when vaccine antigen production is limited, as for example during a pandemic influenza outbreak. We earlier showed that GPI-0100, a semi-synthetic saponin derivative with amphiphilic structure, significantly stimulates the immunogenicity and protective efficacy of influenza subunit vaccine administered via a systemic route. Here, we evaluated the adjuvant effect of GPI-0100 on a virosomal influenza vaccine formulation. In contrast to influenza subunit vaccine adjuvanted with GPI-0100, virosomal vaccine supplemented with the same dose of GPI-0100 provided full protection of mice against infection at the extremely low antigen dose of 2 × 8 ng hemagglutinin. Overall, adjuvanted virosomes elicited higher antibody and T-cell responses than did adjuvanted subunit vaccine. The enhanced immunogenicity of the GPI-0100-adjuvanted virosomes, particularly at low antigen doses, is possibly due to a physical association of the amphiphilic adjuvant with the virosomal membrane. These results show that a combination of GPI-0100 and a virosomal influenza vaccine formulation is highly immunogenic and allows the use of very low antigen doses without compromising the protective potential of the vaccine.

摘要

佐剂可以刺激疫苗引起的免疫反应,并在疫苗抗原产生受到限制时(例如在流感大流行期间),为节省抗原剂量做出决定性贡献。我们之前的研究表明,GPI-0100 是一种具有两亲性结构的半合成皂苷衍生物,可显著增强通过全身途径给药的流感亚单位疫苗的免疫原性和保护效力。在这里,我们评估了 GPI-0100 对病毒样流感疫苗制剂的佐剂作用。与用 GPI-0100 佐剂的流感亚单位疫苗不同,用相同剂量的 GPI-0100 补充的病毒样疫苗在极低的 2×8ng 血凝素抗原剂量下,完全保护了小鼠免受感染。总的来说,佐剂化的病毒样体制剂比佐剂化的亚单位疫苗引起更高的抗体和 T 细胞反应。GPI-0100 佐剂化的病毒样体制剂的免疫原性增强,特别是在低抗原剂量下,可能是由于亲脂性佐剂与病毒样膜的物理结合。这些结果表明,GPI-0100 和病毒样流感疫苗制剂的组合具有高度的免疫原性,并且可以使用非常低的抗原剂量而不损害疫苗的保护潜力。

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