Wu Xueling, Sambor Anna, Nason Martha C, Yang Zhi-Yong, Wu Lan, Zolla-Pazner Susan, Nabel Gary J, Mascola John R
Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
Virology. 2008 Oct 25;380(2):285-95. doi: 10.1016/j.virol.2008.07.007. Epub 2008 Sep 18.
To better understand the limits of antigenic reactivity and epitope accessibility of the V3 domain of primary HIV-1 isolates, we evaluated three human anti-V3 monoclonal antibodies (mAbs) and selected guinea pig vaccine sera for neutralization against reference panels of subtype B and C pseudoviruses derived from early stage infections. The mAbs and vaccine sera potently neutralized several prototype viruses, but displayed substantially less neutralization of most reference strains. In the presence of soluble CD4 (sCD4), the breadth of V3-mediated neutralization was increased; up to 80% and 77% of the subtype B and C viruses respectively were sensitive to V3-mediated neutralization. Unlike sCD4, the reaction of CD4-binding site mAbs b12 and F105 with native virus did not lead to full exposure of the V3 domain. These findings confirm that V3 antibodies recognize most primary viral strains, but that the epitope often has limited accessibility in the context of native envelope spike.
为了更好地理解原发性HIV-1分离株V3结构域的抗原反应性和表位可及性的局限性，我们评估了三种人抗V3单克隆抗体（mAb），并选择豚鼠疫苗血清针对源自早期感染的B型和C型假病毒参考株进行中和试验。这些单克隆抗体和疫苗血清能有效中和多种原型病毒，但对大多数参考毒株的中和作用明显较弱。在可溶性CD4（sCD4）存在的情况下，V3介导的中和作用广度增加；分别有高达80%和77%的B型和C型病毒对V3介导的中和作用敏感。与sCD4不同，CD4结合位点单克隆抗体b12和F105与天然病毒的反应并未导致V3结构域完全暴露。这些发现证实，V3抗体可识别大多数原发性病毒株，但在天然包膜刺突的背景下，表位的可及性通常有限。
