Science for Life Laboratory, Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden;
The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
J Immunol. 2014 Jun 15;192(12):5802-12. doi: 10.4049/jimmunol.1301898. Epub 2014 May 14.
Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1.
近年来，我们对中和抗体（NAb）识别广泛 HIV-1 株（bNAb）的结合位点的了解有了很大的提高。然而，我们对于如何将 B 细胞反应集中到 HIV-1 包膜糖蛋白（Env）中易受影响的保守位点上，仍然存在理解上的差距。在本文中，我们报告了一种免疫策略，由三价 HIV-1（clade B Env）DNA 初免和 SIVmac239 gp140 Env 蛋白加强免疫组成，旨在将免疫反应集中到 HIV-1 和猿猴免疫缺陷病毒（SIV）Env 的结构保守部分上。在兔子中，三价 HIV-1 env 初免诱导的异源 NAb 滴度，主要针对 1 型 HIV-1 分离株，通过 SIVmac239 gp140 蛋白加强免疫显著增加。Ab 结合反应的表位作图显示了对 C1、C2、V2、V3 和 V5 区域的优先识别。这些结果提供了一个概念验证，即远距离相关的逆转录病毒 SIV Env 蛋白加强免疫可以增加针对 HIV-1 的预先存在的 NAb 反应。
