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Annual and Interim Progress Report Summaries

Principal Investigator: Thomas Hope

Project: Antibody-Mucus Interactions

Submitted July 1, 2012

The goal of the Hope CAVD project was to determine if and how the interaction of antibodies with mucus could function to provide protection from HIV acquisition. Key to this mechanism of action is the demonstration that antibodies could interact with cervical and cervicovaginal mucus. We are pleased to report that during the first year of this project we have identified multiple pieces of evidence that IgG can interact with cervical and cervicovaginal mucus. Rather than a mechanism of multiple low affinity interactions, we find that antibodies bind to mucins tightly and potentially with unanticipated specificities. Likewise, we find that IgA binds well to cervical and cervicovaginal mucus. Functional studies with endogenous dimeric IgA with secretory component purified from the breast milk of HIV infected women can potently inhibit HIV transport in mucus. In other studies we have found that a component of cervicovaginal mucus contains slows the relative transport of HIV compared to control nanobeads. This demonstrates the complexity of the interactions of HIV with mucus and provides an important baseline for defining the role of antibodies in decreasing virus transport. Additionally, we are developing a cohort of HIV positive and negative women donors. Preliminary data using over 40 mucosal samples from HIV positive donors suggests that the menstrual cycle has an influence on virus transport. Interestingly, we find that mid-cycle mucus, which is most permissive for fertilization, also has the ability to potently inhibit HIV transport. In contrast luteal phase mucus may have less ability to inhibit virus transport. Initial proteomics studies are beginning to determine how mucus changes during the menstrual cycle and how these changes can influence virus transport. Together, these studies are providing a new window into the interactions that take place between HIV and the mucosal barriers of the female reproductive tract

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