Characterization of a Large Panel of Rabbit Monoclonal Antibodies against HIV-1 gp120 and Isolation of Novel Neutralizing Antibodies against the V3 Loop |
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| Authors: | Yali Qin Saikat Banerjee Aditi Agrawal Heliang Shi Marisa Banasik Feng Lin Kari Rohl Celia LaBranche David C. Montefiori Michael W. Cho |
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| Affiliation: | 1. Department of Biomedical Sciences, Iowa State University, Ames, IA, 50011, United States of America.; 2. Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, Ames, IA, 50011, United States of America.; 3. Department of Surgery, Duke University, Durham, NC, 27710, United States of America.; Shanghai Medical College, Fudan University, CHINA, |
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| Abstract: | 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. |
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