Science：针对HIV-1病毒gp120可能设计更广谱疫苗

刊登在近日的国际杂志Science上的一篇研究报告中，来自国外的研究人员设计了一种免疫原,它代表了朝着制造一种可在人体内释放对抗HIV-1的广谱中和抗体疫苗所迈出的重要的第一步。

Joseph Jardine及其同事对近些年来在世界各地的病人体内分离出的这种高度有效的广谱中和抗体——它对HIV-1的gp120包膜蛋白具有特异性——进行了研究。

研究人员接着想出了一种方法来设计可与这些高度变异的广谱中和抗体结合的gp120蛋白，以及可与那些未变异的前体版本抗体结合的gp120蛋白。他们说，他们新设计的叫做eOD-GT6的免疫原显示其有希望成为一种疫苗引物，且他们的方法也可应用于其它的蛋白和病原体。

doi:10.1126/science.1234150
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Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors

Joseph Jardine1,2,3,4,*, Jean-Philippe Julien2,3,5,*, Sergey Menis1,2,3,4,*, Takayuki Ota1, Oleksandr Kalyuzhniy1,2,3,4, Andrew McGuire6, Devin Sok1,2,3, Po-Ssu Huang4, Skye MacPherson1,2,3,4, Meaghan Jones1,2,4, Travis Nieusma2,3,5, John Mathison1, David Baker4, Andrew B. Ward2,3,5, Dennis R. Burton1,2,3,7, Leonidas Stamatatos6,8, David Nemazee1, Ian A. Wilson2,3,5,9, William R. Schief1,2,3,4,†

Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1–infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors and elucidated germline-binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens.

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