Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity.

Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity.
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DOI:
10.1016/j.vaccine.2010.02.006
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发表时间:
2010-04-09
期刊:
影响因子:
5.5
通讯作者:
Lu, Shan
Lu, Shan
中科院分区:
医学3区
文献类型:
--
作者:
Vaine, Michael;Wang, Shixia;Hackett, Anthony;Arthos, James;Lu, Shan

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使用人类免疫缺陷病毒-1(HIV-1)JR-FL株的gp 120包膜糖蛋白作为模型抗原,本研究的目的是评价不同初免-加强免疫接种方案(仅蛋白质、仅DNA、DNA加蛋白质)在家兔中引起的抗体应答的水平和质量。我们的数据表明,与仅用蛋白质的免疫相比,将DNA免疫作为初免并入异源初免加强方案中能够引发更多样化和构象的表位谱、更高的抗体亲合力和改善的中和活性。此外,尽管当仅使用DNA疫苗接种时观察到类似的抗体特异性和亲合力,但观察到这种改善的中和活性,这提供了使用组合免疫方案增加保护性抗体应答的额外证据。从目前的研究中获得的见解证实,异源DNA引物-蛋白加强方法不仅可以有效地引发高水平的抗原特异性抗体应答,而且可以提高抗原特异性抗体应答的质量,从而为开发更好和更安全的亚单位疫苗提供新的技术平台。
Using a gp120 envelope glycoprotein from the JR-FL strain of human immunodeficiency virus-1 (HIV-1) as a model antigen, the goal of the current study was to evaluate the level and quality of antibody responses elicited by different prime-boost vaccination regimens (protein only, DNA only, DNA plus protein) in rabbits. Our data demonstrated that incorporating DNA immunization as a prime in a heterologous prime boost regimen was able to elicit a more diverse and conformational epitope profile, higher antibody avidity, and improved neutralizing activity than immunization with only protein. Additionally, this improved neutralizing activity was observed in spite of similar antibody specificities and avidities seen when only DNA vaccination was used, providing additional evidence that the use of a combination immunization regimen increases the protective antibody response. Insights gained from the current study confirmed that the heterologous DNA prime-protein boost approach is effective in eliciting not only high level but also improved quality of antigen-specific antibody responses, and thus may offer a new technology platform to develop better and safer subunit vaccines.
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