Das Supratik, Boliar Saikat, Samal Sweety, Ahmed Shubbir, Shrivastava Tripti, Shukla Brihaspati N, Goswami Sandeep, Bansal Manish, Chakrabarti Bimal K
THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad 121001, Haryana, India.
THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad 121001, Haryana, India; IAVI Neutralizing Antibody Center at TSRI, La Jolla, CA, USA.
Virology. 2017 Oct;510:22-28. doi: 10.1016/j.virol.2017.07.001. Epub 2017 Jul 6.
Efficient cleavage of HIV-1 Env gp160 into its constituent subunits correlates with selective binding to neutralizing antibodies and are the closest mimetic of native, functional Envs. This was first demonstrated with the clade B Env, JRFL. The correlation between efficient cleavage and selective binding to neutralizing antibodies is the guiding principle for immunogen design for HIV vaccine. We have recently reported that Envs 4-2.J41 (clade C) and JRCSF (clade B) are also efficiently cleaved and show similar properties. However, an efficiently cleaved, membrane-bound clade A Env suitable for genetic vaccination has not been directly demonstrated. Here we report that BG505 and a new clade A Env, QB726.70M.ENV.C4 (or A5) are efficiently cleaved on cell membrane. A5 shows desirable antigenic properties comparable with BG505 on cell surface. A5SOSIP in supernatant displays majority of bNAb binding epitopes. Thus, both BG505 and A5 Envs can be used in DNA prime-protein boost vaccination studies.
将HIV-1包膜糖蛋白gp160有效切割成其组成亚基，与中和抗体的选择性结合相关，并且是天然功能性包膜最接近的模拟物。这首先在B亚型包膜蛋白JRFL中得到证实。有效切割与中和抗体选择性结合之间的相关性是HIV疫苗免疫原设计的指导原则。我们最近报道，4-2.J41（C亚型）和JRCSF（B亚型）包膜蛋白也能被有效切割，并表现出相似的特性。然而，尚未直接证明一种适合基因疫苗接种的、能被有效切割的膜结合A亚型包膜蛋白。在此我们报道，BG505和一种新的A亚型包膜蛋白QB726.70M.ENV.C4（或A5）在细胞膜上能被有效切割。A5在细胞表面显示出与BG505相当的理想抗原特性。上清液中的A5SOSIP展示了大多数广谱中和抗体结合表位。因此，BG505和A5包膜蛋白均可用于DNA初免-蛋白质加强疫苗接种研究。
