HIV-1 疫苗的组成部分介导病毒样颗粒（VLP）的形成和展示暴露广泛中和表位的包膜蛋白。

Components of a HIV-1 vaccine mediate virus-like particle (VLP)-formation and display of envelope proteins exposing broadly neutralizing epitopes.

机构信息

Research Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH Köln - University of Applied Sciences, Chempark Leverkusen E28, Kaiser-Wilhelm-Allee, 51368, Leverkusen, Germany; Institute of Technical Chemistry, Leibniz University Hannover, Callinstraße 5, 30167, Hannover, Germany.

Research Group Process Engineering, Faculty of Applied Natural Sciences, TH Köln - University of Applied Sciences, Chempark Leverkusen E28, Kaiser-Wilhelm-Allee, 51368, Leverkusen, Germany; Institute of Technical Chemistry, Leibniz University Hannover, Callinstraße 5, 30167, Hannover, Germany.

出版信息

Virology. 2022 Mar;568:41-48. doi: 10.1016/j.virol.2022.01.008. Epub 2022 Jan 22.

DOI:10.1016/j.virol.2022.01.008

PMID:35101772

Abstract

The sequence diversity of HIV-1 is the biggest hurdle for the design of a prophylactic vaccine. Mosaic (Mos) antigens consisting of synthetically shuffled epitopes from various HIV-1 strains are currently tested in the clinical vaccine trial Mosaico (NCT03964415). Besides adenovirus vectors encoding variants of Mos.Gag-Pol and soluble Mos.Env proteins, the Mosaico vaccine entails vectors mediating gene transfer and expression of the membrane-anchored Env-variant Mos2S.Env. We thus examined whether the expression of mosaic Gag mediates the formation of virus-like particles (VLPs). Mos1.Gag- and Mos2.Gag-VLP-formation was readily detected using Western blot- and electron microscopic-analysis. Upon co-expression of both mosaic Gag variants with Mos2S.Env, incorporation of Env into Gag-formed VLPs was observed. The display of the respective neutralization-sensitive target epitopes on Mos2S.Env-decorated VLPs was demonstrated employing a panel of broadly neutralizing antibodies (bNAbs) in a VLP-capture assay. This opens new perspectives for future HIV vaccine designs.

摘要

HIV-1 的序列多样性是设计预防性疫苗的最大障碍。目前正在临床试验 Mosaico（NCT03964415）中测试由来自各种 HIV-1 株的合成重排表位组成的嵌合（Mos）抗原。除了编码 Mos.Gag-Pol 和可溶性 Mos.Env 蛋白变体的腺病毒载体外，Mosaico 疫苗还需要介导基因转移和膜锚定 Env 变体 Mos2S.Env 表达的载体。因此，我们研究了嵌合 Gag 的表达是否介导病毒样颗粒（VLPs）的形成。使用 Western blot 和电子显微镜分析很容易检测到 Mos1.Gag 和 Mos2.Gag-VLP 的形成。当同时表达两种嵌合 Gag 变体与 Mos2S.Env 时，观察到 Env 掺入到 Gag 形成的 VLPs 中。通过在 VLP 捕获测定中使用一组广泛中和抗体（bNAb），证明了各自的中和敏感靶表位在 Mos2S.Env 装饰的 VLPs 上的展示。这为未来的 HIV 疫苗设计开辟了新的前景。