Saunders Kevin O, Wang Lingshu, Joyce M Gordon, Yang Zhi-Yong, Balazs Alejandro B, Cheng Cheng, Ko Sung-Youl, Kong Wing-Pui, Rudicell Rebecca S, Georgiev Ivelin S, Duan Lijie, Foulds Kathryn E, Donaldson Mitzi, Xu Ling, Schmidt Stephen D, Todd John-Paul, Baltimore David, Roederer Mario, Haase Ashley T, Kwong Peter D, Rao Srinivas S, Mascola John R, Nabel Gary J
J Virol. 2015 Aug;89(16):8334-45. doi: 10.1128/JVI.00908-15.
Broadly neutralizing antibodies (bnAbs) can prevent lentiviral infection in nonhuman primates and may slow the spread of human immunodeficiency virus type 1 (HIV-1). Although protection by passive transfer of human bnAbs has been demonstrated in monkeys, durable expression is essential for its broader use in humans. Gene-based expression of bnAbs provides a potential solution to this problem, although immune responses to the viral vector or to the antibody may limit its durability and efficacy. Here, we delivered an adeno-associated viral vector encoding a simianized form of a CD4bs bnAb, VRC07, and evaluated its immunogenicity and protective efficacy. The expressed antibody circulated in macaques for 16 weeks at levels up to 66 g/ml, although immune suppression with cyclosporine (CsA) was needed to sustain expression. Gene-delivered simian VRC07 protected against simian-human immunodeficiency virus (SHIV) infection in monkeys 5.5 weeks after treatment. Gene transfer of an anti-HIV antibody can therefore protect against infection by viruses that cause AIDS in primates when the host immune responses are controlled.
广泛中和抗体（bnAbs）可在非人灵长类动物中预防慢病毒感染，并可能减缓人类免疫缺陷病毒1型（HIV-1）的传播。尽管已在猴子中证明通过被动转移人类bnAbs可提供保护，但持久表达对于其在人类中的更广泛应用至关重要。基于基因的bnAbs表达为解决这一问题提供了一种潜在的解决方案，尽管对病毒载体或抗体的免疫反应可能会限制其持久性和疗效。在此，我们递送了一种编码CD4bs bnAb VRC07猿化形式的腺相关病毒载体，并评估了其免疫原性和保护效果。尽管需要用环孢素（CsA）进行免疫抑制以维持表达，但表达的抗体在猕猴体内循环了16周，水平高达66μg/ml。基因递送的猿猴VRC07在治疗后5.5周可保护猴子免受猿猴-人类免疫缺陷病毒（SHIV）感染。因此，当宿主免疫反应得到控制时，抗HIV抗体的基因转移可保护灵长类动物免受导致艾滋病的病毒感染。
