Department of Chemistry, Brandeis University, Waltham, Massachusetts, USA.
Nat Chem Biol. 2014 Dec;10(12):990-9. doi: 10.1038/nchembio.1685.
Although efforts to develop a vaccine against HIV have so far met with little success, recent studies of HIV-positive patients with strongly neutralizing sera have shown that the human immune system is capable of producing potent and broadly neutralizing antibodies (bnAbs), some of which neutralize up to 90% of HIV strains. These antibodies bind conserved vulnerable sites on the viral envelope glycoprotein gp120, and identification of these sites has provided exciting clues about the design of potentially effective vaccines. Carbohydrates have a key role in this field, as a large fraction of bnAbs bind carbohydrates or combinations of carbohydrate and peptide elements on gp120. Additionally, carbohydrates partially mask some peptide surfaces recognized by bnAbs. The use of engineered glycoproteins and other glycostructures as vaccines to elicit antibodies with broad neutralizing activity is therefore a key area of interest in HIV vaccine design.
虽然目前针对 HIV 开发疫苗的努力收效甚微,但最近对具有强烈中和作用血清的 HIV 阳性患者的研究表明,人体免疫系统能够产生强效且广泛中和的抗体(bnAbs),其中一些能够中和多达 90%的 HIV 毒株。这些抗体结合在病毒包膜糖蛋白 gp120 上的保守脆弱位点,对这些位点的鉴定为设计潜在有效疫苗提供了令人兴奋的线索。碳水化合物在这一领域起着关键作用,因为很大一部分 bnAbs 结合 gp120 上的碳水化合物或碳水化合物和肽元素的组合。此外,碳水化合物部分掩盖了 bnAbs 识别的一些肽表面。因此,使用工程糖蛋白和其他糖结构作为疫苗来诱导具有广泛中和活性的抗体是 HIV 疫苗设计的一个关键研究领域。