Qin Yali, Banerjee Saikat, Agrawal Aditi, Shi Heliang, Banasik Marisa, Lin Feng, Rohl Kari, LaBranche Celia, Montefiori David C, Cho Michael W
Department of Biomedical Sciences, Iowa State University, Ames, IA, 50011, United States of America; Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, Ames, IA, 50011, United States of America.
Department of Surgery, Duke University, Durham, NC, 27710, United States of America.
PLoS One. 2015 Jun 3;10(6):e0128823. doi: 10.1371/journal.pone.0128823. eCollection 2015.
We recently reported the induction of potent, cross-clade neutralizing antibodies (nAbs) against Human Immunodeficiency Virus type-1 (HIV-1) in rabbits using gp120 based on an M-group consensus sequence. To better characterize these antibodies, 93 hybridomas were generated, which represent the largest panel of monoclonal antibodies (mAbs) ever generated from a vaccinated rabbit. The single most frequently recognized epitope of the isolated mAbs was at the very C-terminal end of the protein (APTKAKRRVVEREKR), followed by the V3 loop. A total of seven anti-V3 loop mAbs were isolated, two of which (10A3 and 10A37) exhibited neutralizing activity. In contrast to 10A3 and most other anti-V3 loop nAbs, 10A37 was atypical with its epitope positioned more towards the C-terminal half of the loop. To our knowledge, 10A37 is the most potent and broadly neutralizing anti-V3 loop mAb induced by vaccination. Interestingly, all seven anti-V3 loop mAbs competed with PGT121, suggesting a possibility that early induction of potent anti-V3 loop antibodies could prevent induction of more broadly neutralizing PGT121-like antibodies that target the conserved base of the V3 loop stem.
我们最近报道了基于M组共有序列，利用gp120在兔体内诱导出针对1型人类免疫缺陷病毒（HIV-1）的强效、跨亚型中和抗体（nAbs）。为了更好地表征这些抗体，我们制备了93个杂交瘤，这代表了从接种疫苗的兔体内产生的最大一组单克隆抗体（mAbs）。分离出的mAbs中最常识别的单一表位位于该蛋白的最C末端（APTKAKRRVVEREKR），其次是V3环。总共分离出7个抗V3环mAbs，其中两个（10A3和10A37）表现出中和活性。与10A3和大多数其他抗V3环nAbs不同，10A37是非典型的，其表位更靠近环的C末端一半。据我们所知，10A37是由疫苗诱导产生的最有效且广谱中和的抗V3环mAb。有趣的是，所有7个抗V3环mAbs都与PGT121竞争，这表明早期诱导强效抗V3环抗体可能会阻止诱导出更多靶向V3环茎部保守碱基的广谱中和的PGT121样抗体。
