title: Inhibition of HIV-1 infectivity and epithelial cell transfer by human monoclonal IgG and IgA antibodies carrying the b12 V region.
abstract: Both IgG and secretory IgA Abs in mucosal secretions have been implicated in blocking the earliest events in HIV-1 transit across epithelial barriers, although the mechanisms by which this occurs remain largely unknown. In this study, we report the production and characterization of a human rIgA(2) mAb that carries the V regions of IgG1 b12, a potent and broadly neutralizing anti-gp120 Ab which has been shown to protect macaques against vaginal simian/HIV challenge. Monomeric, dimeric, polymeric, and secretory IgA(2) derivatives of b12 reacted with gp120 and neutralized CCR5- and CXCR4-tropic strains of HIV-1 in vitro. With respect to the protective effects of these Abs at mucosal surfaces, we demonstrated that IgG1 b12 and IgA(2) b12 inhibited the transfer of cell-free HIV-1 from ME-180 cells, a human cervical epithelial cell line, as well as Caco-2 cells, a human colonic epithelial cell line, to human PBMCs. Inhibition of viral transfer was due to the ability of b12 to block both viral attachment to and uptake by epithelial cells. These data demonstrate that IgG and IgA MAbs directed against a highly conserved epitope on gp120 can interfere with the earliest steps in HIV-1 transmission across mucosal surfaces, and reveal a possible mechanism by which b12 protects the vaginal mucosal against viral challenge in vivo.
authors: Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12208, USA. nmantis@wadsworth.org
authors: Nicholas J
authors: NJ
authors: Mantis
authors: Jana
authors: J
authors: Palaia
authors: Ann J
authors: AJ
authors: Hessell
authors: Simren
authors: S
authors: Mehta
authors: Zhiyi
authors: Z
authors: Zhu
authors: Blaise
authors: B
authors: Corthésy
authors: Marian R
authors: MR
authors: Neutra
authors: Dennis R
authors: DR
authors: Burton
authors: Edward N
authors: EN
authors: Janoff
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D015483:HIV Antibodies / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D011994:Recombinant Proteins
references: J Pathol. 2006 Jan;208(2):270-82
references: 16362985
references: Curr Mol Med. 2003 May;3(3):217-28
references: 12699359
references: Nat Rev Microbiol. 2003 Oct;1(1):25-34
references: 15040177
references: Immunity. 2002 Jul;17(1):107-15
references: 12150896
references: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4215-20
references: 12642661
references: J Virol. 2004 Dec;78(23):13232-52
references: 15542675
references: Curr Protoc Protein Sci. 2004 Nov;Chapter 3:3.1.1-3.1.9
references: 18429266
references: AIDS Res Hum Retroviruses. 2002 Nov 20;18(17):1291-300
references: 12487817
references: J Virol. 2001 Sep;75(17):8340-7
references: 11483779
references: J Infect Dis. 1998 Aug;178(2):431-40
references: 9697723
references: Immunology. 1982 Oct;47(2):383-5
references: 7118169
references: J Immunol Methods. 1985 Mar 18;77(2):305-19
references: 3981007
references: Virology. 2002 Jul 5;298(2):306-16
references: 12127792
references: AIDS Res Hum Retroviruses. 2003 Jul;19(7):597-607
references: 12908937
references: Mol Immunol. 1993 Mar;30(4):413-21
references: 8455639
references: J Infect Dis. 2001 Apr 15;183(8):1204-13
references: 11262202
references: Science. 1994 Nov 11;266(5187):1024-7
references: 7973652
references: Nat Immunol. 2004 Mar;5(3):233-6
references: 14985706
references: J Immunol Methods. 1990 Aug 7;131(2):195-202
references: 2391428
references: J Immunol. 1995 Jul 15;155(2):707-14
references: 7608548
references: J Virol. 2003 Apr;77(7):4095-103
references: 12634368
references: Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3029-34
references: 10077631
references: Nat Med. 2000 Feb;6(2):200-6
references: 10655110
references: Curr Opin Immunol. 2002 Aug;14(4):495-502
references: 12088685
references: Nat Med. 2002 Feb;8(2):150-6
references: 11821899
references: Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2700-4
references: 8464878
references: Infect Immun. 1997 Apr;65(4):1387-94
references: 9119478
references: J Virol. 2000 Jun;74(12):5577-86
references: 10823865
references: Nat Med. 2005 Apr;11(4 Suppl):S45-53
references: 15812489
references: J Virol. 2007 Jan;81(1):395-405
references: 17050597
references: J Virol. 1990 May;64(5):2416-20
references: 2325207
references: J Immunol. 2001 Nov 1;167(9):5185-92
references: 11673531
references: Biotechnology (N Y). 1992 Feb;10(2):169-75
references: 1369477
references: Nature. 2005 Apr 28;434(7037):1093-7
references: 15793563
references: J Immunol Methods. 1986 Jan 22;86(1):83-7
references: 3944471
references: J Immunol. 1993 Nov 1;151(9):4743-52
references: 8409433
references: Scand J Immunol. 2000 Sep;52(3):240-8
references: 10972899
references: J Immunol. 2005 Nov 15;175(10):6694-701
references: 16272325
references: J Virol. 2004 Jun;78(12):6567-84
references: 15163749
references: Science. 2001 Aug 10;293(5532):1155-9
references: 11498595
references: Nat Immunol. 2006 Mar;7(3):235-9
references: 16482171
references: J Immunol. 2004 Aug 1;173(3):1978-86
references: 15265932
references: AIDS. 2003 Mar 28;17(5):685-9
references: 12646791
references: Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12559-63
references: 7809077
references: Nat Med. 2000 Feb;6(2):207-10
references: 10655111
references: J Immunol. 2000 Feb 15;164(4):1952-60
references: 10657645
references: J Immunol. 1991 Oct 1;147(7):2130-5
references: 1918947
references: J Acquir Immune Defic Syndr. 2000 Aug 1;24(4):297-309
references: 11015145
references: Nat Med. 2003 Mar;9(3):343-6
references: 12579198
references: Virology. 2004 Aug 1;325(2):389-98
references: 15246277