Development of Gram Stain Scoring System Based on Pro-Inflammatory Cytokines in the Sheep Model for Testing Toxicity of Vaginal Products.

Development of safe, effective products to prevent the sexual transmission of HIV remains a priority. Prior to clinical testing, the products must undergo strict safety evaluations to avoid mucosal drug toxicity, inflammation, and vaginal microbiome (VMB) shifts. Based on the Food and Drug Administration (FDA) guidance, we designed a study to measure the inflammatory markers and VMB changes after intravaginal treatment with products that have been associated with toxicity, with the objective to develop a Gram stain slide scoring system, similar to Nugent scoring, correlated with the proinflammatory cytokines in sheep.

Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation.

The development of therapies targeted to improve the health of women has utilized direct vaginal delivery as a more effective and less toxic method of protection from HIV and other pathogens. Vaginal applicants and delivery devices that provide sustained effects have been met with increasing acceptability, but the efficacy and toxicity outcomes have not been successfully predicted by preclinical studies and animal modeling. We have explored the utilization of sheep as a model for testing the safety of vaginal applicants and devices based on spatial and structural similarities to the human vagina.

Development of an IgG-Fc fusion COVID-19 subunit vaccine, AKS-452.

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs.

Efficacy of a Nanofabricated Electrospun Wound Matrix in Treating Full-thickness Cutaneous Wounds in a Porcine Model.

Objective: This study aims to evaluate the comparative performance of a resorbable nanofiber wound matrix (Restrata Wound Matrix; Acera Surgical Inc, St Louis, MO) and a bilayered collagen xenograft (Integra Bilayer Matrix Wound Dressing; Integra, Plainsboro, NJ) in healing critical full-thickness cutaneous wounds in a preclinical porcine model.

Materials And Methods: Full-thickness cutaneous wounds were created in Yucatan miniature swine and treated with either the nanofiber wound matrix or xenograft. Wound area was measured and inflammation and healing were assessed until euthanasia at day 15 or 30, at which time tissue samples were harvested for histopathology.

Comparison of a microsphere-based platform with a multiplex flow cytometric assay for determination of circulating cytokines in the mouse.

Background: Measuring expression profiles of inflammatory biomarkers is important in monitoring the polarization of immune responses; therefore, results should be independent of quantitation methods if they are to be accepted as validated clinical pathology biomarkers. To evaluate effects of differing quantitation methods, the seven major circulating Th1/Th2/Th17 cytokines interleukin 2 (IL-2), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), IL-4, IL-6, IL-10 and IL-17A were quantified in plasma of lipopolysaccharide (LPS)-treated mice with two different multiplex platforms.

Methods: Female C57BL6 mice were treated orally with vehicle or dexamethasone, followed by LPS intravenously.

Local and systemic effects of a silver nitrate coated indwelling pleural catheter in an animal model of pleurodesis.

Unlabelled: Purpose/Aim of the study: This study assessed the safety and potential toxicity of a silver nitrate coated indwelling pleural catheter (SNCIPC) designed to create pleurodesis in a large animal model.

Materials And Methods: Sixteen animals underwent insertion of either a SNCIPC or an uncoated silicone catheter. Half of the animals were sacrificed at day 7 and the others at day 30.

Comparison of a Fully Synthetic Electrospun Matrix to a Bi-Layered Xenograft in Healing Full Thickness Cutaneous Wounds in a Porcine Model.

A fully synthetic electrospun matrix was compared to a bi-layered xenograft in the healing of full thickness cutaneous wounds in Yucatan miniature swine. Full thickness wounds were created along the dorsum, to which these matrices were applied. The wound area was measured over the course of healing and wound tissue was scored for evidence of inflammation and healing.

Development of a Functional Observational Battery in the Minipig for Regulatory Neurotoxicity Assessments.

A functional observational battery (FOB) is recommended as the first-tier neurotoxicity screening in the preclinical safety pharmacology testing guidelines. Minipigs have increasingly been used in regulatory toxicology studies; however, no current FOB protocol is available for neurotoxicity testing in these species. Hence, a minipig FOB instrument was developed.

The importance of minipigs in dermal safety assessment: an overview.

The use of miniature swine as a non-rodent species in safety assessment has continued to expand for over a decade and their use has become routine, particularly in pharmacology as a model for human integumentary diseases. Translational preclinical swine study data are now favorably compared and contrasted to human data, and miniature swine models provide important information in dermal safety assessment and skin pharmacology. For example, the miniature swine model has been well-accepted for cutaneous absorption and toxicity studies due to swine integument being morphologically and functionally similar to human skin.

The Miniature Swine as a Model in Experimental and Translational Medicine.

The use of the miniature swine as a nonrodent species in research has continued to expand for over a decade, and they are becoming routinely used both in experimental pharmacology and as a therapeutic model for human diseases. Miniature swine models are regularly used for studies designed to assess efficacy and safety of new therapeutic compounds given through different routes of exposure and are used as an alternative model to rodents, canines, or nonhuman primates. Translational preclinical swine study data presented here support the current understanding that miniature swine are the animal model of choice for the assessment of drugs targeting endocrine, dermal, and ocular disorders.

Pigs in Toxicology: Breed Differences in Metabolism and Background Findings.

Both a rodent and a nonrodent species are required for evaluation in nonclinical safety studies conducted to support human clinical trials. Historically, dogs and nonhuman primates have been the nonrodent species of choice. Swine, especially the miniature swine or minipigs, are increasingly being used in preclinical safety as an alternate nonrodent species.

Miniature Swine Breeds in Toxicology and Drug Safety Assessments: What to Expect during Clinical and Pathology Evaluations.

The use of miniature swine as a nonrodent species in safety assessment has continued to expand for over a decade, and they are becoming routinely used in toxicology and in pharmacology as well as a model for human diseases. Miniature swine models are regularly used for regulatory toxicity studies designed to assess safety of new therapeutic compounds given through different routes of exposure and are used as an alternative model to the canine or the nonhuman primate. Translational preclinical swine study data presented support the current finding that miniature swine are the animal model of choice for assessment of drug absorption, tolerance, and systemic toxicity following systemic exposures.

Background Pathological Changes in Minipigs: A Comparison of the Incidence and Nature among Different Breeds and Populations of Minipigs.

Swine, especially the miniature swine or minipigs, are increasingly being used in preclinical safety assessment of small molecules, biopharmaceutical agents, and medical devices as an alternate nonrodent species. Although swine have been used extensively in biomedical research, there is a paucity of information in the current literature detailing the incidence of background lesions and differences in incidence between commonly used breeds. This article is a collaborative effort between multiple organizations to define and document lesions found in the common breeds of minipigs used for toxicological risk assessment in North America (NA) and the European Union (EU).

Miniature swine model of phototoxicity testing.

Background/purpose: This study determined the threshold doses for 'solar erythema' and for phototoxic responses to 8-methoxypsoralen (8-MOP) in white skin Hanford and grey skin Yucatan miniature swine.

Methods: For threshold erythema determinations, the UVR exposures included both UVA (315-400 nm) and UVB (290-315 nm) radiation by positioning one fluorescent 'sunlamp' among 10 'PUVA' lamps. With this configuration the UVR exposures ranged from 0.

Retrospective evaluation of production characteristics in Sinclair miniature swine--44 years later.

Three hundred seventy-one litter records collected between 1985 and 1993 from 156 Sinclair S-1 miniature sows, a Hormel-derived strain of miniature swine, were retrospectively analyzed and compared with published records for 1950 to 1952 and 1963 to 1965. The effect of several variables such as season and month of parturition, age of sow, parity, and litter size on reproductive parameters of the Sinclair miniature swine were evaluated. The mean and standard error of the mean for litter size, number of liveborn, number of stillborn, and litter size at weaning of the Sinclair S-1 miniature swine were 7.