Wednesday, January 27, 2016

Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection

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.

Below:  Distribution of analyte concentrations in cervicovaginal lavage samples for 370 healthy visits

Full article at:

Suzanna C. Francis, Kathy Baisley, Trong T. Ao, Saidi Kapiga, Richard J. Hayes
MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom

Suzanna C. Francis, Deborah Watson-Jones, Trong T. Ao, Kaballa Maganja, Aura Andreasen, Saidi Kapiga
Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania, United Republic of Tanzania

Yanwen Hou, Gary R. Coulton
Division of Basic Medical Sciences, St. George's Medical School, University of London, London, United Kingdom

Janneke van de Wijgert
Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom

Carolina Herrera, Robin J. Shattock
Mucosal Infection and Immunity Group, Imperial College, Department of Medicine, London, United Kingdom

Deborah Watson-Jones, Aura Andreasen
Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom

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