在这项新的研究中，来自美国国家卫生研究院（NIH）、贝斯以色列女执事医疗中心、拉根研究所、洛斯阿拉莫斯国家实验室和斯克里普斯研究所的研究人员利用这种组合抗体注射策略让一组实验室猴子完全免受HIV感染。在组合抗体注射时，他们是将两种HIV抗体（即PGT121和PGDM1400）的混合物接种到这些猴子体内。相关研究结果发表在2017年9月20日的Science Translational Medicine期刊上，论文标题为“Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail”。
作者: ipsvirus 时间: 2017-9-22 13:12 Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail
Boris Julg1,2,*, Po-Ting Liu1,*, Kshitij Wagh3, William M. Fischer3, Peter Abbink1, Noe B. Mercado1, James B. Whitney1,2, Joseph P. Nkolola1, Katherine McMahan1, Lawrence J. Tartaglia1, Erica N. Borducchi1, Shreeya Khatiwada1, Megha Kamath1, Jake A. LeSuer1, Michael S. Seaman1, Stephen D. Schmidt4, John R. Mascola4, Dennis R. Burton2,5, Bette T. Korber3 and Dan H. Barouch
HIV-1 sequence diversity presents a major challenge for the clinical development of broadly neutralizing antibodies (bNAbs) for both therapy and prevention. Sequence variation in critical bNAb epitopes has been observed in most HIV-1–infected individuals and can lead to viral escape after bNAb monotherapy in humans. We show that viral sequence diversity can limit both the therapeutic and prophylactic efficacy of bNAbs in rhesus monkeys. We first demonstrate that monotherapy with the V3 glycan-dependent antibody 10-1074, but not PGT121, results in rapid selection of preexisting viral variants containing N332/S334 escape mutations and loss of therapeutic efficacy in simian-HIV (SHIV)–SF162P3–infected rhesus monkeys. We then show that the V3 glycan-dependent antibody PGT121 alone and the V2 glycan-dependent antibody PGDM1400 alone both fail to protect against a mixed challenge with SHIV-SF162P3 and SHIV-325c. In contrast, the combination of both bNAbs provides 100% protection against this mixed SHIV challenge. These data reveal that single bNAbs efficiently select resistant viruses from a diverse challenge swarm to establish infection, demonstrating the importance of bNAb cocktails for HIV-1 prevention.