刊登在近日的國際雜志Science上的一篇研究報(bào)告中,，來自國外的研究人員設(shè)計(jì)了一種免疫原,它代表了朝著制造一種可在人體內(nèi)釋放對(duì)抗HIV-1的廣譜中和抗體疫苗所邁出的重要的第一步,。
Joseph Jardine及其同事對(duì)近些年來在世界各地的病人體內(nèi)分離出的這種高度有效的廣譜中和抗體——它對(duì)HIV-1的gp120包膜蛋白具有特異性——進(jìn)行了研究,。
研究人員接著想出了一種方法來設(shè)計(jì)可與這些高度變異的廣譜中和抗體結(jié)合的gp120蛋白,，以及可與那些未變異的前體版本抗體結(jié)合的gp120蛋白,。他們說,，他們新設(shè)計(jì)的叫做eOD-GT6的免疫原顯示其有希望成為一種疫苗引物,，且他們的方法也可應(yīng)用于其它的蛋白和病原體。（生物谷Bioon.com）
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.
