Format

Send to

Choose Destination
AIDS Res Hum Retroviruses. 2018 Apr;34(4):365-374. doi: 10.1089/AID.2017.0250. Epub 2018 Jan 25.

Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller.

Author information

1
1 Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy , Frankfurt, Germany .
2
2 Department of Infectious Diseases, HIV Center, University Hospital , Frankfurt, Germany .
3
3 Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris) , Paris, France .

Abstract

The analysis of patient derived HIV neutralizing antibodies (nAbs) and their target epitopes in the viral envelope (Env) protein provides important basic information for vaccine design. In this study we optimized an epitope, EC26-2A4, that is targeted by neutralizing antibodies from an elite controller (EC26) and localizes in the membrane-proximal external region from the gp41 transmembrane protein. Due to its overlap with the epitope of the first generation broadly neutralizing monoclonal Ab (mAb) 2F5 associated with autoreactivity, we first defined the minimal core epitope reacting with antibodies from EC26 plasma, but not with mAb 2F5. The optimized minimal epitope, EC26-2A4ΔM, was able to induce neutralizing antibodies in vaccinated mice. We further analyzed the frequency of antibodies against the EC26-2A4ΔM peptide in HIV-positive patient sera from a treated cohort and an untreated long-term nonprogressor (LTNP) cohort. Interestingly, 27% of the LTNP sera reacted with the peptide, whereas only 9% showed reactivity in the treated cohort. Although there was no association between the presence of antibodies against the EC26-2A4ΔM epitope and viral load or CD4 count in these patients, the CD4 nadir in the treated cohort was higher in patients positive for EC26-2A4ΔM antibodies, in particular in patients having such antibodies at an early and a late timepoint after infection.

KEYWORDS:

Env; HIV-1; MPER; epitope; gp41; neutralizing antibodies

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center