Malebo Kegomoditswe, Woodward Jeremy, Ximba Phindile, Mkhize Qiniso, Cingo Sanele, Moyo-Gwete Thandeka, Moore Penny L, Williamson Anna-Lise, Chapman Rosamund
Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
Vaccines (Basel). 2024 Sep 18;12(9):1063. doi: 10.3390/vaccines12091063.
Despite treatment and other interventions, an effective prophylactic HIV vaccine is still an essential goal in the control of HIV. Inducing robust and long-lasting antibody responses is one of the main targets of an HIV vaccine. The delivery of HIV envelope glycoproteins (Env) using nanoparticle (NP) platforms has been shown to elicit better immunogenicity than soluble HIV Env. In this paper, we describe the development of a nanoparticle-based vaccine decorated with HIV Env using the SpyCatcher/SpyTag system. The Env utilised in this study, CAP255, was derived from a transmitted founder virus isolated from a patient who developed broadly neutralising antibodies. Negative stain and cryo-electron microscopy analyses confirmed the assembly and stability of the mi3 into uniform icosahedral NPs surrounded by regularly spaced CAP255 gp140 Env trimers. A three-dimensional reconstruction of CAP255 gp140 SpyTag-SpyCatcher mi3 clearly showed Env trimers projecting from the centre of each of the pentagonal dodecahedral faces of the NP. To our knowledge, this is the first study to report the formation of SpyCatcher pentamers on the dodecahedral faces of mi3 NPs. To investigate the immunogenicity, rabbits were primed with two doses of DNA vaccines expressing the CAP255 gp150 and a mosaic subtype C Gag and boosted with three doses of the NP-developed autologous Tier 2 CAP255 neutralising antibodies (Nabs) and low levels of heterologous CAP256SU NAbs.
尽管有治疗和其他干预措施,但有效的预防性HIV疫苗仍是控制HIV的一个重要目标。诱导强大而持久的抗体反应是HIV疫苗的主要目标之一。使用纳米颗粒(NP)平台递送HIV包膜糖蛋白(Env)已被证明比可溶性HIV Env具有更好的免疫原性。在本文中,我们描述了一种使用SpyCatcher/SpyTag系统开发的用HIV Env修饰的基于纳米颗粒的疫苗。本研究中使用的Env,CAP255,源自从一名产生广泛中和抗体的患者分离出的传播奠基病毒。负染色和冷冻电子显微镜分析证实了mi3组装成均匀的二十面体NP,并被规则间隔的CAP255 gp140 Env三聚体包围。CAP255 gp140 SpyTag-SpyCatcher mi3的三维重建清楚地显示Env三聚体从NP的每个五角十二面体表面的中心突出。据我们所知,这是第一项报道在mi3 NPs的十二面体表面形成SpyCatcher五聚体的研究。为了研究免疫原性,用两剂表达CAP255 gp150和嵌合C亚型Gag的DNA疫苗对兔子进行免疫,并用三剂NP开发的自体2级CAP255中和抗体(Nabs)和低水平的异源CAP256SU Nabs进行加强免疫。