title: Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection.
abstract: Soluble cervicovaginal biomarkers of inflammation, immune activation and risk of HIV acquisition are needed to reliably assess the safety of new biomedical prevention strategies including vaccines and microbicides. However, a fuller understanding of expression profiles in women at high risk for HIV infection is crucial to the effective use of these potential biomarkers in Phase 3 trial settings. We have measured 45 soluble proteins and peptides in cervicovaginal lavage samples from 100 HIV negative women at high risk for HIV infection. Women were followed over one menstrual cycle to investigate modulation by hormonal contraception, menstrual cycle phase, recent sexual exposure and intravaginal practices. Women using injectable DMPA had increased concentration of several soluble proteins of the innate and adaptive immune system, including IL-1α, IL-1β, IL-2, MIP-1β, IP-10, IL-8, TGF-β, HBD4, IgA, IgG1, and IgG2. Women using combined oral contraceptives had a similar signature. There were differences in concentrations among samples from post-ovulation compared to pre-ovulation, notably increased immunoglobulins. Increased prostate-specific antigen, indicative of recent sexual exposure, was correlated with increased IL-6, MCP-1, and SLPI, and decreased GM-CSF and HBD3. The identified signature profiles may prove critical in evaluating the potential safety and impact on risk of HIV acquisition of different biomedical intervention strategies.
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.|Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania, United Republic of Tanzania.
authors.forename: Suzanna C
authors.initials: SC
authors.lastname: Francis
authors.affiliation: Division of Basic Medical Sciences, St. George's Medical School, University of London, London, United Kingdom.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Hou
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Kathy
authors.initials: K
authors.lastname: Baisley
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Janneke
authors.initials: J
authors.lastname: van de Wijgert
authors.affiliation: Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania, United Republic of Tanzania.|Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Deborah
authors.initials: D
authors.lastname: Watson-Jones
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.|Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania, United Republic of Tanzania.
authors.forename: Trong T
authors.initials: TT
authors.lastname: Ao
authors.affiliation: Mucosal Infection and Immunity Group, Imperial College, Department of Medicine, London, United Kingdom.
authors.forename: Carolina
authors.initials: C
authors.lastname: Herrera
authors.affiliation: Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania, United Republic of Tanzania.
authors.forename: Kaballa
authors.initials: K
authors.lastname: Maganja
authors.affiliation: Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania, United Republic of Tanzania.|Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Aura
authors.initials: A
authors.lastname: Andreasen
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.|Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania, United Republic of Tanzania.
authors.forename: Saidi
authors.initials: S
authors.lastname: Kapiga
authors.affiliation: Division of Basic Medical Sciences, St. George's Medical School, University of London, London, United Kingdom.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Coulton
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hayes
authors.affiliation: Mucosal Infection and Immunity Group, Imperial College, Department of Medicine, London, United Kingdom.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
mesh_terms: D000293:Adolescent; D000328:Adult; D000814:Aniline Compounds / Q000008:administration & dosage; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage; D016207:Cytokines / Q000032:analysis* / Q000378:metabolism; D003710:Demography; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007136:Immunoglobulins / Q000032:analysis*; D007962:Leukocytes / Q000166:cytology; D008597:Menstrual Cycle; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000302:isolation & purification; D017430:Prostate-Specific Antigen / Q000032:analysis; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D060737:Reproductive Tract Infections / Q000175:diagnosis / Q000235:genetics / Q000382:microbiology; D012306:Risk; D018139:Simplexvirus / Q000235:genetics / Q000302:isolation & purification; D014621:Vagina / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D044364:Vaginal Douching; D055815:Young Adult
chemical_list: D000814:Aniline Compounds; D003278:Contraceptives, Oral, Hormonal; D016207:Cytokines; D006454:Hemoglobins; D007136:Immunoglobulins; D012336:RNA, Ribosomal, 16S; C050795:N,N-dimethyl-4-anisidine; D017430:Prostate-Specific Antigen
references.citation: Infect Immun. 1999 Dec;67(12):6321-8
references.pmid: 10569744
references.citation: J Interferon Cytokine Res. 2000 Aug;20(8):719-24
references.pmid: 10954915
references.citation: J Infect Dis. 2001 Aug 15;184(4):418-28
references.pmid: 11471099
references.citation: Infect Immun. 2001 Sep;69(9):5840-8
references.pmid: 11500462
references.citation: AIDS. 2001 Aug 17;15(12):1535-43
references.pmid: 11504986
references.citation: J Reprod Med. 1984 Apr;29(4):269-71
references.pmid: 6716372
references.citation: J Reprod Med. 1989 Apr;34(4):292-4
references.pmid: 2715991
references.citation: J Infect Dis. 2009 Aug 15;200(4):599-608
references.pmid: 19586414
references.citation: Nat Med. 2009 Aug;15(8):886-92
references.pmid: 19648930
references.citation: J Reprod Immunol. 2009 Dec;83(1-2):185-9
references.pmid: 19850356
references.citation: Clin Vaccine Immunol. 2015 May;22(5):526-38
references.pmid: 25761460
references.citation: Am J Reprod Immunol. 2015 Oct;74(4):357-67
references.pmid: 26202107
references.citation: Science. 2010 Sep 3;329(5996):1168-74
references.pmid: 20643915
references.citation: J Clin Microbiol. 1991 Feb;29(2):297-301
references.pmid: 1706728
references.citation: Environ Health Perspect. 1996 Apr;104(4):408-13
references.pmid: 8732951
references.citation: Contraception. 1999 Mar;59(3):195-201
references.pmid: 10382083
references.citation: J Forensic Sci. 1999 Sep;44(5):1057-60
references.pmid: 10486959
references.citation: Cell Tissue Res. 2005 Oct;322(1):43-52
references.pmid: 15909166
references.citation: J Acquir Immune Defic Syndr. 2004 Oct;37 Suppl 3:S184-93
references.pmid: 16419271
references.citation: Hum Reprod. 2006 Jun;21(6):1442-52
references.pmid: 16439502
references.citation: Contraception. 2006 Aug;74(2):133-40
references.pmid: 16860051
references.citation: AIDS. 2007 Feb 19;21(4):467-76
references.pmid: 17301565
references.citation: AIDS. 2007 Mar 12;21(5):589-98
references.pmid: 17314521
references.citation: Blood. 2007 May 15;109(10):4272-9
references.pmid: 17289812
references.citation: Sex Transm Infect. 2007 Dec;83(7):505-8
references.pmid: 18024709
references.citation: J Acquir Immune Defic Syndr. 2008 Feb 1;47(2):253-7
references.pmid: 18025996
references.citation: N Engl J Med. 2008 Apr 10;358(15):1560-71
references.pmid: 18337596
references.citation: Lancet. 2008 Nov 29;372(9653):1881-93
references.pmid: 19012954
references.citation: AIDS. 2009 Jan 28;23(3):319-28
references.pmid: 19114867
references.citation: J Acquir Immune Defic Syndr. 2008 Dec 15;49(5):520-2
references.pmid: 18989228
references.citation: Sex Transm Dis. 2009 Mar;36(3 Suppl):S84-91
references.pmid: 19218890
references.citation: N Engl J Med. 2009 Dec 3;361(23):2209-20
references.pmid: 19843557
references.citation: PLoS One. 2010;5(2):e9119
references.pmid: 20161749
references.citation: Nature. 2010 Mar 11;464(7286):217-23
references.pmid: 20220840
references.citation: PLoS Med. 2010 Jun;7(6):e1000287
references.pmid: 20543994
references.citation: Lancet. 2010 Oct 16;376(9749):1329-37
references.pmid: 20851460
references.citation: J Reprod Immunol. 2011 Jan;88(1):66-71
references.pmid: 21051089
references.citation: N Engl J Med. 2010 Dec 30;363(27):2587-99
references.pmid: 21091279
references.citation: PLoS Med. 2011;8(2):e1000416
references.pmid: 21358808
references.citation: Cytokine. 2011 Jul;55(1):134-40
references.pmid: 21530305
references.citation: Lancet Infect Dis. 2011 Jul;11(7):507-15
references.pmid: 21570355
references.citation: Contraception. 2011 Nov;84(5):512-9
references.pmid: 22018127
references.citation: J Acquir Immune Defic Syndr. 2012 Feb 1;59(2):134-40
references.pmid: 22067666
references.citation: J Immunol. 2012 Mar 1;188(5):2445-54
references.pmid: 22271649
references.citation: J Infect Dis. 2012 Jul 15;206(2):258-66
references.pmid: 22561365
references.citation: N Engl J Med. 2012 Aug 2;367(5):399-410
references.pmid: 22784037
references.citation: N Engl J Med. 2012 Aug 2;367(5):423-34
references.pmid: 22784038
references.citation: PLoS One. 2012;7(8):e43951
references.pmid: 22952818
references.citation: Endocrinology. 2013 Mar;154(3):1282-95
references.pmid: 23354099
references.citation: AIDS Res Hum Retroviruses. 2013 Mar;29(3):592-601
references.pmid: 23189932
references.citation: PLoS One. 2013;8(3):e59085
references.pmid: 23555618
references.citation: Lancet. 2013 Jun 15;381(9883):2083-90
references.pmid: 23769234
references.citation: PLoS One. 2013;8(7):e68825
references.pmid: 23874780
references.citation: J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):109-17
references.pmid: 24413042
references.citation: Am J Reprod Immunol. 2014 Aug;72(2):171-81
references.pmid: 24661500
references.citation: PLoS Med. 2015 Jan;12(1):e1001778
references.pmid: 25612136