Detailed characterization of antibody responses against HIV-1 group M consensus gp120 in rabbits

Retrovirology

Michael W Cho¹  Marisa Banasik¹  Aditi Agrawal¹  Saikat Banerjee¹  Heliang Shi¹  Yali Qin¹ 

[1] Center for Advanced Host Defenses, Immunobiotics and Translational Comparative Medicine, Iowa State University, Ames 50011, IA, USA

关键词: Antibody competition;    Immunogenic epitope;    SOSIP gp140;    gp120;    eOD-GT6;    Neutralizing antibody;    HIV-1 vaccine;   

Others  :  1132011
DOI  :  10.1186/s12977-014-0125-5

 received in 2014-10-24, accepted in 2014-12-04,  发布年份 2014

【 摘 要 】

Background

We recently reported induction of broadly neutralizing antibodies (bnAbs) against multiple HIV-1 (human immunodeficiency virus type 1) isolates in rabbits, albeit weak against tier 2 viruses, using a monomeric gp120 derived from an M group consensus sequence (MCON6). To better understand the nature of the neutralizing activity, detailed characterization of immunological properties of the protein was performed. Immunogenic linear epitopes were identified during the course of immunization, and spatial distribution of these epitopes was determined. Subdomain antibody target analyses were done using the gp120 outer domain (gp120-OD) and eOD-GT6, a protein based on a heterologous sequence. In addition, refined epitope mapping analyses were done by competition assays using several nAbs with known epitopes.

Results

Based on linear epitope mapping analyses, the V3 loop was most immunogenic, followed by C1 and C5 regions. The V1/V2 loop was surprisingly non-immunogenic. Many immunogenic epitopes were clustered together even when they were distantly separated in primary sequence, suggesting the presence of immunogenic hotspots on the protein surface. Although substantial antibody responses were directed against the outer domain, only about 0.1% of the antibodies bound eOD-GT6. Albeit weak, antibodies against peptides that corresponded to a part of the bnAb VRC01 binding site were detected. Although gp120-induced antibodies could not block VRC01 binding to eOD-GT6, they were able to inhibit VRC01 binding to both gp120 and trimeric BG505 SOSIP gp140. The immune sera also efficiently competed with CD4-IgG2, as well as nAbs 447-52D, PGT121 and PGT126, in binding to gp120.

Conclusions

The results suggest that some antibodies that bind at or near known bnAb epitopes could be partly responsible for the breadth of neutralizing activity induced by gp120 in our study. Immunization strategies that enhance induction of these antibodies relative to others (e.g. V3 loop), and increase their affinity, could improve protective efficacy of an HIV-1 vaccine.

【 授权许可】

   
2014 Qin et al.; licensee BioMed Central.

【 图 表 】

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