Date on Master's Thesis/Doctoral Dissertation

8-2013

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Committee Chair

Palmer, Kenneth Edward

Author's Keywords

Microbicides; Immunogenility; Lectin; HIV

Subject

Anti-infective agents; Lectins

Abstract

Griffithsin (GRFT) is a protein derived from the red alga Griffithsia sp. off the coast of New Zealand. It binds and inactivates number of enveloped viruses including HIV-1. For a product to be developed as a microbicide, it must be safe and effective after repeated use. For initial in vivo safety testing we exposed mice repeatedly to various vaginal products and found that increased concentration of mouse serum albumin (MSA) in the vaginal lumen is predictive of epithelial damage. Repeated intravaginal administration of GRFT did not result in increased amounts of MSA, but the known epithelial disrupters nonoxynol-9 and benzylkonium chloride caused increased concentrations of MSA that were detectable by ELISA and western blot. We also evaluated the immunogenicity of GRFT following repeated exposure and found that intravaginal administration resulted in higher serum IgG antibody titers, but not local IgA or IgG levels, than did subcutaneous administration. The consequences of the systemic immune response are unknown and require further investigation.

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