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Michael Swanson University of North Carolina

Protein engineering of the lectin BanLec reduces its mitogenic activity and prevents vaginal HIV transmission. Michael Swanson University of North Carolina. Engineering BanLec to Reduce its Mitogenic and Stimulatory Activity. BanLec binds to high-mannose on gp120

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Michael Swanson University of North Carolina

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  1. Protein engineering of the lectin BanLec reduces its mitogenic activity and prevents vaginal HIV transmission Michael Swanson University of North Carolina

  2. Engineering BanLec to Reduce its Mitogenic and Stimulatory Activity • BanLec binds to high-mannose on gp120 • Broad, potent activity anti-HIV activity • Microbicide Candidate • Can its stimulatory activity be reduced? • Substitution of amino acids in binding sites Strategy Outline • cDNA for BanLec • Introduce amino substitutions Express in E. coli • Purify variants • Assess stimulatory activity TFV 3.2 µM

  3. Topically-applied BanLec H84T Prevents Vaginal HIV Transmission Apply 75 µg BanLec H84T Topically Expose Vaginally with HIV-1JR-CSF 10 minutes later • Measure Viral Load p=0.0359

  4. Conclusions • BanLec H84T has reduced mitogenicity and is effective ant preventing vaginal HIV transmission in vivo • BanLec H84T should be investigated as a potential microbicide. • Engineering of mitogenic, anti-HIV lectins could lead to more microbicide candidates

  5. Acknowledgements University of Leuven, Rega Institute for Medical Research -Dominique Schols -Dana Huskens University of Michigan -David Markovitz -Dan Bodreaux University of North Carolina -J. Victor Garcia NIH Grants: AI100775

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