Brady Jacqueline M, Baltimore David, Balazs Alejandro B
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Immunol Rev. 2017 Jan;275(1):324-333. doi: 10.1111/imr.12478.
Broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) show great promise in HIV prevention as they are capable of potently neutralizing a considerable breadth of genetically diverse strains. Passive transfer of monoclonal bNAb proteins can confer protection in animal models of HIV infection at modest concentrations, inspiring efforts to develop an HIV vaccine capable of eliciting bNAb responses. However, these antibodies demonstrate high degrees of somatic mutation and other unique characteristics that may hinder the ability of conventional approaches to consistently and effectively produce bNAb analogs. As an alternative strategy, we and others have proposed vector-mediated gene transfer to generate long-term, systemic production of bNAbs in the absence of immunization. Herein, we review the use of adeno-associated virus (AAV) vectors for delivery of HIV bNAbs and antibody-like proteins and summarize both the advantages and disadvantages of this strategy as a method for HIV prevention.
针对人类免疫缺陷病毒（HIV）的广泛中和抗体（bNAbs）在HIV预防方面显示出巨大潜力，因为它们能够有效中和相当广泛的基因多样化毒株。单克隆bNAb蛋白的被动转移在适度浓度下可在HIV感染动物模型中提供保护，这激发了开发能够引发bNAb反应的HIV疫苗的努力。然而，这些抗体表现出高度的体细胞突变和其他独特特征，这可能会阻碍传统方法持续有效地生产bNAb类似物的能力。作为一种替代策略，我们和其他人提出了载体介导的基因转移，以在不进行免疫的情况下长期、全身性地产生bNAbs。在此，我们综述了腺相关病毒（AAV）载体用于递送HIV bNAbs和抗体样蛋白的情况，并总结了该策略作为HIV预防方法的优缺点。
