Broadly Neutralizing Monoclonal Antibodies 2F5 and 4E10 Directed against the Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Protect against Mucosal Challenge by Simian-Human Immunodeficiency Virus SHIVBa-L
Broadly Neutralizing Monoclonal Antibodies 2F5 and 4E10 Directed against the Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Protect against Mucosal Challenge by Simian-Human Immunodeficiency Virus SHIVBa-L
复制标题
DOI：
10.1128/jvi.01272-09
复制
发表时间：
2010-02-01
影响因子：
5.4
通讯作者：
Burton, Dennis R.
中科院分区：
文献类型：
--
作者：
Hessell, Ann J.;Rakasz, Eva G.;Burton, Dennis R.
HIV-1的膜近端外部区（MPER）位于gp 41胞外域的C末端，是保守的，对病毒融合至关重要。三种广泛中和的单克隆抗体（bnMAb），2F 5、4 E10和Z13 e1，针对定位于MPER的线性表位，使得该保守区域成为重要的潜在疫苗靶标。然而，没有MPER抗体已经明确显示出提供针对HIV攻击的保护。在这里，我们表明，这两个单克隆抗体2F 5和4 E10可以提供完整的保护粘膜猴-人免疫缺陷病毒（SHIV）的挑战，在猕猴。在用SHIVBa-L直肠内激发前1天和直肠内激发后1天，将MAb 2F 5或4 E10以50 mg/kg静脉内给予每组6只雄性印度恒河猴。在两组中，6只动物中有5只显示出完全保护和杀菌免疫，而每组中有1只动物在攻毒后病毒复制水平较低，不能排除这种情况。该研究证实了2F 5和4 E10的保护潜力，并支持强调基于gp 41的MPER区域的HIV免疫原设计。
The membrane-proximal external region (MPER) of HIV-1, located at the C terminus of the gp41 ectodomain, is conserved and crucial for viral fusion. Three broadly neutralizing monoclonal antibodies (bnMAbs), 2F5, 4E10, and Z13e1, are directed against linear epitopes mapped to the MPER, making this conserved region an important potential vaccine target. However, no MPER antibodies have been definitively shown to provide protection against HIV challenge. Here, we show that both MAbs 2F5 and 4E10 can provide complete protection against mucosal simian-human immunodeficiency virus (SHIV) challenge in macaques. MAb 2F5 or 4E10 was administered intravenously at 50 mg/kg to groups of six male Indian rhesus macaques 1 day prior to and again 1 day following intrarectal challenge with SHIVBa-L. In both groups, five out of six animals showed complete protection and sterilizing immunity, while for one animal in each group a low level of viral replication following challenge could not be ruled out. The study confirms the protective potential of 2F5 and 4E10 and supports emphasis on HIV immunogen design based on the MPER region of gp41.