title: 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.
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Elin S
authors.initials: ES
authors.lastname: Gray
authors.forename: Maphuti C
authors.initials: MC
authors.lastname: Madiga
authors.forename: Penny L
authors.initials: PL
authors.lastname: Moore
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.forename: Salim S
authors.initials: SS
authors.lastname: Abdool Karim
authors.forename: James M
authors.initials: JM
authors.lastname: Binley
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D000906:Antibodies / Q000097:blood / Q000276:immunology; D018604:Epitope Mapping; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018189:Immunomagnetic Separation; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary
chemical_list: D000906:Antibodies; D015700:HIV Envelope Protein gp41
references.citation: J Virol. 2009 Sep;83(17):8451-62
references.pmid: 19515770
references.citation: J Virol. 2008 Mar;82(5):2367-75
references.pmid: 18094155
references.citation: J Virol. 2005 Jan;79(2):1252-61
references.pmid: 15613352
references.citation: Science. 2005 Jun 24;308(5730):1906-8
references.pmid: 15860590
references.citation: Immunity. 2008 Jan;28(1):52-63
references.pmid: 18191596
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9057-62
references.pmid: 19458040
references.citation: J Virol. 2009 Jan;83(2):757-69
references.pmid: 18987148
references.citation: J Virol. 2009 Jan;83(2):1045-59
references.pmid: 19004942
references.citation: J Virol. 1999 Mar;73(3):2469-80
references.pmid: 9971832
references.citation: J Infect Dis. 1997 Oct;176(4):924-32
references.pmid: 9333150
references.citation: J Virol. 2007 Jun;81(12):6187-96
references.pmid: 17409164
references.citation: J Virol. 2009 Sep;83(17):8925-37
references.pmid: 19553335
references.citation: Curr Opin HIV AIDS. 2009 Sep;4(5):364-72
references.pmid: 20048699
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4144-9
references.pmid: 12644702
references.citation: J Virol. 2009 Apr;83(8):3617-25
references.pmid: 19193787
references.citation: J Virol. 2009 Aug;83(15):7397-410
references.pmid: 19458010
references.citation: Curr Pharm Des. 2007;13(2):213-27
references.pmid: 17269929
references.citation: J Intern Med. 2007 Jul;262(1):26-43
references.pmid: 17598813
references.citation: J Virol. 2001 Nov;75(22):10892-905
references.pmid: 11602729
references.citation: J Virol. 2001 Jul;75(14):6558-65
references.pmid: 11413323
references.citation: J Virol. 2004 Dec;78(23):13232-52
references.pmid: 15542675
references.citation: AIDS. 2005 Nov 4;19(16):1725-37
references.pmid: 16227780
references.citation: Biotechnol Bioeng. 2000 Jan 5;67(1):97-103
references.pmid: 10581440
references.citation: AIDS Res Hum Retroviruses. 2004 Jul;20(7):755-62
references.pmid: 15307922
references.citation: J Virol. 2007 Apr;81(8):4033-43
references.pmid: 17287272
references.citation: J Virol. 2004 Oct;78(19):10724-37
references.pmid: 15367639
references.citation: J Virol. 1997 May;71(5):3734-41
references.pmid: 9094648
references.citation: PLoS One. 2008 Apr 16;3(4):e1954
references.pmid: 18414658
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3739-44
references.pmid: 18322015
references.citation: J Virol. 2006 Mar;80(6):3030-41
references.pmid: 16501112
references.citation: Nat Med. 2009 Aug;15(8):866-70
references.pmid: 19525964
references.citation: AIDS. 2006 Oct 3;20(15):1923-30
references.pmid: 16988513
references.citation: J Virol. 2003 May;77(10):5678-84
references.pmid: 12719560
references.citation: AIDS. 2002 Feb 15;16(3):501-3
references.pmid: 11834970
references.citation: J Virol. 2009 Jan;83(1):188-99
references.pmid: 18922865
references.citation: J Virol. 2008 Dec;82(23):11651-68
references.pmid: 18815292
references.citation: PLoS Med. 2006 Jul;3(7):e255
references.pmid: 16834457
references.citation: Curr Protoc Immunol. 2005 Jan;Chapter 12:12.11.1-12.11.17
references.pmid: 18432938