Topical gel formulation of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 confers protection against HIV-1 vaginal challenge in a humanized mouse model.

Topical gel formulation of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 confers protection against HIV-1 vaginal challenge in a humanized mouse model.
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广泛中和抗 HIV-1 单克隆抗体 VRC01 的局部凝胶制剂可在人源化小鼠模型中提供针对 HIV-1 阴道攻击的保护作用。

DOI:
10.1016/j.virol.2012.06.025
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Akkina,Ramesh
Akkina,Ramesh
中科院分区:
医学3区
文献类型:
--
作者:
Veselinovic,Milena;Neff,CPreston;Mulder,LeilaR;Akkina,Ramesh

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抗HIV-1的新一代广泛中和抗体VRC 01显示出作为局部施用的杀微生物剂预防性传播的巨大潜力。我们在阴道HIV-1传播的RAG-hu人源化小鼠模型中评估了其功效。在阴道内施用VRC 01(1 mg/ml浓度)凝胶后1小时,用R5嗜性HIV-1 BaL阴道攻击小鼠。四种第一代bNAb,即b12、2F 5、4 E10和2G 12的组合用作阳性功效对照,而非特异性登革MAb 4G 2用作阴性对照。我们的结果显示,9只施用VRC 01抗体的小鼠中有7只和所有接受4种bNAb抗体组合的小鼠都受到保护,免受HIV-1攻击。这些发现证明了新的bNAb VRC 01作为局部杀微生物剂预防HIV-1阴道传播的有效性,并强调了RAG-hu小鼠模型用于测试HIV预防策略的用途。
The new generation broadly neutralizing antibody VRC01 against HIV-1 shows great potential as a topically administered microbicide to prevent sexual transmission. We evaluated its efficacy in a RAG-hu humanized mouse model of vaginal HIV-1 transmission. Mice were challenged vaginally with R5 tropic HIV-1 BaL an hour after intravaginal application of the VRC01 (1mg/ml concentration) gel. A combination of four first generation bNAbs, namely b12, 2F5, 4E10 and 2G12, was used as a positive efficacy control whereas a non-specific dengue MAb 4G2 was used as negative control. Our results showed that seven out of nine VRC01 antibody administered mice and all of the mice receiving the four bNAb antibody combination were protected against HIV-1 challenge. These findings demonstrate the efficacy of the new bNAb VRC01 as a topical microbicide to protect against HIV-1 vaginal transmission and highlight the use of the RAG-hu mouse model for testing HIV prevention strategies.
人和大鼠周围神经的游离脂肪酸组成。
DOI: 10.1111/j.1471-4159.1981.tb01720.x
发表时间: 1981
影响因子: 4.7
作者:
Yao,JK;Dyck,PJ;VanLoon,JA;Moyer,TP
通讯作者: Moyer,TP