HIV-1 Membrane-Proximal External Region Fused to Diphtheria Toxin Domain-A Elicits 4E10-Like Antibodies in Mice

被引：3

作者：

Zhang, Zhiqing ^{[1
]}

Wei, Xiang ^{[2
]}

Lin, Yanling ^{[2
]}

Huang, Fang ^{[2
]}

Shao, Jia ^{[1
]}

Qi, Jialong ^{[1
]}

Deng, Tingting ^{[2
]}

Li, Zizhen ^{[2
]}

Gao, Shuangquan ^{[1
]}

Li, Shaoyong ^{[1
]}

Yu, Hai ^{[1
]}

Zhao, Qinjian ^{[1
]}

Le, Shaowei ^{[1
,2
]}

Gu, Ying ^{[1
,2
]}

Xia, Ningshao ^{[1
,2
]}

机构：

[1] Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Fujian, Peoples R China

[2] Xiamen Univ, Sch Life Sci, Natl Inst Diagnost & Vaccine Dev Infect Dis, Xiamen 361102, Fujian, Peoples R China

来源：

IMMUNOLOGY LETTERS | 2019年 / 213卷

基金：

中国国家自然科学基金;

关键词：

HIV-1; MPER; Diphtheria toxin domain A; Vaccine; Neutralizing antibodies; NEUTRALIZING ANTIBODIES; V3; LOOP; VACCINE; GP120; GP41; PEPTIDE; FUSION; IMMUNOGENICITY; EPITOPES; BROAD;

D O I：

10.1016/j.imlet.2019.07.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The production of broadly neutralizing antibodies (bNAbs) is a major goal in the development of an HIV-1 vaccine. The membrane-proximal external region (MPER) of gp41, which plays a critical role in the virus membrane fusion process, is highly conserved and targeted by bNAbs 2F5, 4E10, and 10E8. As such, MPER could be a promising epitope for vaccine design. In this study, diphtheria toxin domain A (CRM197, amino acids 1-191) was used as a scaffold to display the 2F5 and 4E10 epitopes of MPER, named CRM197-A-2F5 and CRM197-A-4E10. Modest neutralizing activities were detected against HIV-1 Glade B and D viruses in the sera from mice immunized with CRM197-A-4E10. Monoclonal antibodies raised from CRM197-A-4E10 could neutralize several HIV-1 strains, and epitope-mapping analysis indicated that some antibodies recognized the same amino acids as 4E10. Collectively, we show that 4E10-like antibodies can be induced by displaying MPER epitopes using an appropriate scaffold. These results provide insights for HIV-1 MPER-based immunogens design.

引用

页码：30 / 38

页数：9

共 54 条

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