Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.
Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.
Nat Commun. 2019 May 29;10(1):2355. doi: 10.1038/s41467-019-10262-5.
Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.
我们利用类似于天然 HIV-1 包膜糖蛋白（Env）的稳定蛋白来制定疫苗接种策略，旨在诱导广泛中和抗体（bNAbs）。为了减少罕见的分离株特异性抗原表位/决定簇的暴露，我们基于所有 HIV-1 组 M 分离株的共识序列（ConM）生成了一种 SOSIP 三聚体。ConM 三聚体展示了大多数已知 bNAb 和几种原始 bNAb 前体的表位。分辨率为 3.9Å 的 ConM 三聚体的晶体结构类似于天然 Env 三聚体，其抗原表面很少有稀有残基。ConM 三聚体在兔子和猕猴中引发针对自体病毒的强烈 NAb 反应，当它呈现在铁蛋白纳米颗粒上时，反应会显著增强。主要的 NAb 特异性针对三聚体顶端或附近的一个表位。基于共识序列的免疫原在针对 HIV-1 和其他病毒的疫苗工程中可能具有实用性。
Zotero 插件
