Core C: Virology will support Research Projects I, II and III and Cores B and D through the provision ofspecific reagents, antiviral and other anti-infective evaluations, and efficacy data for the pyrimidinediones,ISIS 5320 oligonucleotide, and NCp7 viral inactivating agents alone and in combination products. Core C willaccomplish these goals by implementation of the following objectives:Objective 1: Primary Antiviral Efficacy and Toxicity Testing: The antiviral efficacy and toxicity data will utilizewhole virus replication assays and specific cellular and biochemical assays to measure the antiviral effects ofthe active microbicide and formulated product based on their defined mechanisms of action. Toxicityevaluations will be performed in parallel for each antiviral measurement. Objective 2: Evaluation of theActivity of Combination Microbicide Products:
The aim of this objective is to utilize standard in vitromicrobicide efficacy assays to evaluate, quantify and prioritize combinations of microbicide products to bedeveloped as long-lasting microbicides for evaluation in ex vivo cervical explant models as well as for furtherdevelopment as gel and ring products. Objective 3: Evaluation of the Effects of Vaginal and Seminal Fluidson Viral Infectivity and Microbicide Efficacy and Toxicity: We will perform in vitro efficacy and toxicityevaluations using seminal plasma and vaginal fluid additives to each of the antiviral assays performed and tofurther define the biological properties of these fluids on viral infectivity, microbicide action, and cellulartoxicity.Objective 4: Development of Microbicide-Resistant Virus Strains and Evaluation of the Ability of theMicrobicides to Inhibit the Transmission of Wild Type and Resistant Virus: We will select for viruses that areresistant to each of the microbicides alone and in combination with one another and evaluate the ability ofthe microbicides to totally suppress the transmission of wild type and resistant viruses.Objective 5: ToxicityEvaluation of Microbicide Products and Formulated Materials: Cell-based in vitro toxicology testing will beperformed utilizing cell lines, relevant Lactobacilli species, and ex vivo tissues. Objective 6: PreclinicalDevelopment of Microbicide Products Alone and In Combination: Lead microbicide products defined by thestudies will be assessed for their antiviral potential consistent with their advancement to clinical testing.
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