Antibody gene transfer with adeno-associated viral vectors as a method for HIV prevention

被引:47
作者
Brady, Jacqueline M. [1 ]
Baltimore, David [2 ]
Balazs, Alejandro B. [1 ]
机构
[1] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA
[2] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA
基金
美国国家卫生研究院;
关键词
adeno-associated virus; antibody gene transfer; broadly neutralizing antibodies; HIV; immunoprophylaxis; IMMUNODEFICIENCY-VIRUS TYPE-1; SITE-SPECIFIC INTEGRATION; NEUTRALIZATION IN-VITRO; MUCOSAL SHIV CHALLENGE; VACCINE EFFICACY TRIAL; FC-RECEPTOR; INTRAMUSCULAR INJECTION; HUMANIZED MICE; TRANSGENE EXPRESSION; SUSTAINED EXPRESSION;
D O I
10.1111/imr.12478
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:324 / 333
页数:10
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