Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region

• DOI: 10.1128/jvi.01359-09
• Publication Date: 2009-08-20T00:48:41Z
• Authors: Elin S. Gray; Maphuti C. Madiga; Penny L. Moore; Koleka Mlisana; Salim S. Abdool K...; James M. Binley; George M. Shaw; John R. Mascola; Lynn Morris
• Keywords: Subclass

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 were directly responsible for the observed neutralization breadth, we used MPER-coated magnetic beads deplete plasmas of specific antibodies. Depletion anti-MPER BB34, CAP206, and SAC21 resulted in 77%, 68%, 46% decreases, respectively, number viruses neutralized. Antibodies eluted showed profiles similar those original plasmas, potencies comparable known monoclonal (MAbs), 4E10, 2F5, Z13e1. The neutralizing BB34 present immunoglobulin G3 subclass-enriched fraction. Alanine scanning MPER that had specificities distinct MAbs, requiring one crucial residues at positions 670, 673, 674. These data demonstrate existence MPER-specific plasma, although ability elicit such potent antiviral during natural infection appears be rare. Nevertheless, identification novel antibody within supports its further study as a promising target vaccine design.