Broad neutralization of human immunodeficiency virus type 1 mediated by plasma antibodies against the gp41 membrane proximal external region.

Abstract

We identified three cross-neutralizing plasma samples with high-titer anti-membrane proximal external

region (MPER) peptide binding antibodies from among 156 chronically human immunodeficiency virus type

1-infected individuals. In order to establish if these antibodies were directly responsible for the observed

neutralization breadth, we used MPER-coated magnetic beads to deplete plasmas of these specific antibodies.

Depletion of anti-MPER antibodies from BB34, CAP206, and SAC21 resulted in 77%, 68%, and 46% decreases,

respectively, in the number of viruses neutralized. Antibodies eluted from the beads showed neutralization

profiles similar to those of the original plasmas, with potencies comparable to those of the known anti-MPER

monoclonal antibodies (MAbs), 4E10, 2F5, and Z13e1. The anti-MPER neutralizing antibodies in BB34 were

present in the immunoglobulin G3 subclass-enriched fraction. Alanine scanning of the MPER showed that the

antibodies from these three plasmas had specificities distinct from those of the known MAbs, requiring one to

three crucial residues at positions 670, 673, and 674. These data demonstrate the existence of MPER-specific

cross-neutralizing antibodies in plasma, although the ability to elicit such potent antiviral antibodies during

natural infection appears to be rare. Nevertheless, the identification of three novel antibody specificities within

the MPER supports its further study as a promising target for vaccine design.