类病毒颗粒展示人免疫缺陷病毒V3抗原诱导小鼠产生跨型中和抗体  

Induction of anti-V3 Cross-Clade Neutralizing Antibody by VLP displaying V3 Immunogens in mice

作　　者：邵佳 乔佳明[2] 高双全 李少勇[2] 李少伟[2] 顾颖[1] Shao Jia;Qiao Jia-ming;Gao Shuang-quan;Li Shao-yong;Li Shao-wei;Gu Ying(Medicine College,Hunan Normal University,Changsha 410013,China;School of Public Health,Xiamen University,State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics,Xiamen 361102,China)

机构地区：[1]湖南师范大学医学院,长沙410013 [2]厦门大学公共卫生学院分子疫苗学和分子诊断学国家重点实验室,厦门361102

出　　处：《湖南师范大学学报（医学版）》2022年第4期7-11,共5页Journal of Hunan Normal University(Medical Sciences)

基　　金：国家自然科学基金(81671645)。

摘　　要：目的:人免疫缺陷病毒1型(HIV-1)感染是获得性免疫缺陷综合征(艾滋病)的主要病因。HIV-1的包膜糖蛋白gp120的第三可变区(V3)对病毒的感染至关重要,本研究旨在探讨V3作为疫苗研制的可能性。方法:本研究将V3_(NL4-3)序列296-311(aa CTRPNNNTRKSIRIQR)插入人乳头瘤病毒(HPV)L1病毒样颗粒(VLPs)中进行融合表达,免疫Balb/c小鼠。随后通过基于免疫斑点印迹法(ELISPOT)的HIV中和筛选平台筛选到表位特异性的小鼠单克隆抗体(mAbs),并通过中和实验和ELISA对单抗进行性质鉴定。结果:筛选到的大多数单克隆抗体只能中和HIV_(NL4-3),可以与多种亚型gp120结合。对不同毒株的中和实验发现,mAb 4H4可以中和实验室现有的毒株。4H4特异识别V3_(NL4-3)的296-305肽段,是V3相对保守的区域。结论:筛选到交叉中和的特异针对V3的单克隆抗体表明,V3-HPVs具有开发成HIV疫苗的潜力。Objective Human immunodeficiency virus type 1(HIV-1) infection is the archcriminal of acquired immunodeficiency syndrome (AIDS).The third variable region (V3) of the gp120 envelope glycoprotein of HIV-1 is critical for the infectivity of the virus.This study is to investigate the possibility of developing a vaccine.Methods A V3 fusion protein containing the V3_(NL4-3) sequence 296-311(aa CTRPNNNTRKSIRIQR) was employed to insert into human papilloma virus (HPV) L1 virus-like particles (VLPs) in this paper.This fusion protein was used to immunize Balb/c mice.Subsequently,epitope-specific mouse monoclonal antibodies (mAbs) were screened by neutralization screening platform based on ELISPOT approach.The mAbs were characterized by HIV neutralization assay and ELISA.Results The most of the mAbs only could neutralize HIV_(NL4-3),they could bind to various subtypes gp120.Neutralization assays to different virus indicated that mAb 4H4 could neutralize the laboratory existing strains.4H4 could specifically recognize the 296-305 peptide of V3_(NL4-3),which is the relatively conserved areas of V3.Conclusion The mAbs aimed at the V3 loop with cross-neutralization indicate that the V3-HPVs have the potential to be developed into a vaccine against HIV.

关 键 词：HIV-1 交叉中和抗体 抗V3抗体 

分 类 号：R392.1[医药卫生—免疫学]