Human immunodeficiency virus-1 vaccine designed based on the natural conformation of the neutralizing epitope in gp41 membrane-proximal external region
CAO Miao1, SU Shan1, YE Ling2, LU Lu1, YANG Qinglai2, JIANG Shibo1
1. Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; 2. Department of Microbiology and Immunology and Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322, USA
Abstract：Vaccine has long been regarded as the most powerful weapon to HIV, including HIV-1 and HIV-2. The membrane-proximal external region (MPER) located at the C-terminus of the extracellular domain of gp41 is a key antigenic site. However, gp41 is not well-exposed on the wild-type HIV-1 particle, and gp41 molecule or a MPER peptides alone cannot simulate the natural conformation of gp120/gp41 envelope protein on the viral membrane. In this study, we designed a series of chimeric HA/gp41-1605 DNA by introduced mutations in the gp41 NHR and CHR regions to block their interaction to form 6-HB and replacing HA1 using those from different influenza A viruses (IAVs) to prevent the production of a large amount of HA1-specific antibodies and to present the native conformation of the HIV-1 gp41 MPER. The results showed that chimeric vaccine antigens expressed on cells exhibited the neutralizing epitopes in MPER, but did not display the immunodominant antigen epitopes on gp41. After the sequential intramuscular immunization of New Zealand Rabbits with these HA/gp41-1605 chimeric DNA vaccines, we found that the chimeric vaccine could not elicit HA-, loop-, and 6-HB-specific antibodies. Although this vaccine can induce MPER-specific antibodies, but not HIV-1 neutralizing antibodies, suggesting that further optimization of this strategy is warranted.
曹妙1，苏珊1，叶玲2，陆路1，杨庆来2，姜世勃1. 基于gp41近膜端外部区域中和表位天然构象的人类免疫缺陷病毒1型疫苗的设计[J]. 微生物与感染, 2021, 16(3): 145-163.
CAO Miao1, SU Shan1, YE Ling2, LU Lu1, YANG Qinglai2, JIANG Shibo1. Human immunodeficiency virus-1 vaccine designed based on the natural conformation of the neutralizing epitope in gp41 membrane-proximal external region. JOURNAL OF MICROBES AND INFECTIONS, 2021, 16(3): 145-163.
2021, Vol. 16 
