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AIDS 2012 T. Blake Ball National Laboratory for HIV Immunology, Public Health Agency Canada

Highly HIV exposed seronegative (HESN) sex workers from Nairobi, Kenya have altered innate mucosal immune responses at the level of the female genital tract. AIDS 2012 T. Blake Ball National Laboratory for HIV Immunology, Public Health Agency Canada

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AIDS 2012 T. Blake Ball National Laboratory for HIV Immunology, Public Health Agency Canada

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  1. Highly HIV exposed seronegative (HESN) sex workers from Nairobi, Kenya have altered innate mucosal immune responses at the level of the female genital tract AIDS 2012 T. Blake Ball National Laboratory for HIV Immunology, Public Health Agency Canada Immunology and Medical Microbiology University of of Manitoba

  2. Resistance to HIV-1 Infection Adapted from Fowke et al Lancet 1996 7 years follow, HIV-1 serology and PCR negative, Active in sex work. 10% of highly exposed sex workers resistant to HIV-1. Decline in HIV-1 Incidence with follow up in the Pumwani Cohort.

  3. Adapted from Fowke et al Lancet 1996 FGT is the source of majority of HIV transmission Worldwide Already remarkably able to block HIV infection as only a minority of virus can breakthru mucosal bottleneck Many Innate factors identified that are thought to inhibit infection (SLPI/RANTES/etc) Unbiased system biology approaches provide insight as to what may be unique in FGT of HIV-R SW’s N=120 N=76 Decline in HIV-1 Incidence with follow up in the Pumwani Cohort.

  4. Specific antiproteases are overexpressed in genital secretions of HIV-R women Cervical lavage

  5. Specific antiproteases are overexpressed in genital secretions of HIV-R women Cervical lavage Gene ontology of 41 (of 400+ identified) differentially expressed proteins in the cervical mucosa of HIV-1-resistant women as identified by mass spectrometry. Overexpressed Underexpressed

  6. Specific antiproteases are overexpressed in genital secretions of HIV-R women Serpin A1 Serpin A3 Cystatin A Cervical lavage P=0.02 P=0.006 P=0.02 P=0.19 P=0.003 P=0.0002 Gene ontology of 41 (of 400+ identified) differentially expressed proteins in the cervical mucosa of HIV-1-resistant women as identified by mass spectrometry. Overexpressed Underexpressed Apo A1 Serpin B3

  7. HIV-resistant women do not have elevated levels of pro-inflammatory cytokines in their cervical mucosa • Specific antiproteases with known anti-inflamatory and anti-HIV activities are overexpressed in the absence of an inflammatory cytokine milieu suggesting a potential mechanism for protection against HIV infection. • Evidence for an Immunoqueiscent state at the FGT? Antiproteases may be ideal candidates for microbicide component • Studies ongoing to determine mechanism of action and regulation of expression at FGT

  8. Immunohistochemical stains of selected antiproteases Cystatin B A2ML1 Serpin A1

  9. Ball Lab Adam Burgener Max Abou Kenzie Mogk Keith Fowke /Julie L UM Frank Plummer PHAC/UM Paul Sandstrom PHAC Garret Westmacott PHAC Kristina Broliden Karolinska Joshua Kimani University of Nairobi Walter Jaoko Omu Anzala Women of the Pumwani, Majengo and Korogocho CSW Clinics, Staff at the WHO Collaborative Center. Nairobi, Kenya

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