Infectious Disease Animal Models
Director: Richard Frothingham, MD

Shared Resource Summary:
The Infectious Disease Animal Models Shared Resource provides animal models to support research in emerging infections and biodefense. The Shared Resource supports animal models using BSL2 and BSL3 pathogens, bacteria and viruses, and a variety of mammalian species and routes of exposure. Aerosol exposures are delivered in collaboration with the Aerobiology Shared Resource. Value is added through collaboration with other DHVI Shared Resources. Microbial burden or host response can be monitored in vivo using the Animal Imaging Shared Resource. Samples from experimental animals can be analyzed in the Research Flow Cytometry and Cell Sorting, or the Immune Reconstitution and Biomarker Analysis Shared Resources.
Personnel/Contact Information:
Director: Richard Frothingham, MD Office Phone: (919) 684 5455 Lab Phone: (919) 260 3768 Fax: (919) 681 1678 Email: richard.frothingham@duke.edu	Manager: Ching-ju Chen, PhD Office Phone: (919) 919 681 1034 Lab Phone: (919) 257 7875 Fax: (919) 681 1678 Email: ching-ju.chen@duke.edu
Location: Global Health Research Building, DUMC Box 103020, Durham, NC 27710
Getting Started:
Contact Richard Frothingham, MD, Shared Resource Director, to initiate your project. We will develop a research plan, then provide a detailed quote for the proposed research. Please see the Common Tools sidebar to register to use facilities, schedule or request a job, and to retrieve data. For a schedule of fees for services, please contact DHVI Shared Resources business office.
Facilities and Instruments:
The BSL3 Animal Models Shared Resource provides animal models to support research in emerging infections and biodefense. The Shared Resource is located within the Regional Biocontainment Laboratory at Duke. This space was designed to satisfy or exceed all BSL3 and ABSL3 requirements under the NIH-CDC Handbook, Biosafety in Microbiological and Biomedical Laboratories, 5th edition. It incorporates the following biosafety and biosecurity enhancements over standard BSL3/ABSL3 standards: Double-door changing room at BSL3 facility entrance for gown-in Individual anterooms for each BSL3 lab and animal suite Shower-out capacity for selected BSL3 rooms, for all ABSL3 suites, and for the BSL3 containment area as a whole Effluent waste treatment for BSL3 containment area Filtration of all supply air for the BSL3 containment area HEPA filtration of all exhaust air from BSL3 containment area Ventilation control system to prevent positive pressurization of BSL3 rooms Autoclaves for each BSL3 lab and animal suite All BSL3 room penetrations confirmed to be sealed (not just sealable) Validated vaporized hydrogen peroxide decontamination sequence for every BSL3 and ABSL3 room. 24-hours armed security presence Advanced security features including reinforced construction, internal and external cameras, perimeter fence, motion detectors, and card-key access control. The BSL3 vivarium is located inside the containment area of the Regional Animal husbandry is carried out by Comparative Medicine Specialists from the Division of Laboratory Animal Resources. The BSL3 vivarium includes the following features and resources: Two independent ABSL3 suites, each with an anteroom, two animal holding areas, and a procedure/aerobiology room, a total of 1800 square feet Animal research support space Shower out capacity within each ABSL3 suites Effluent waste treatment for ABSL3 containment area Redundant bulk autoclaves for animal cages, carcasses, and waste HEPA-filtered negative-pressure cage racks
Services Provided:
The Core will provide comprehensive services related to animal challenge with BSL2 and BSL3 pathogens: Project planning based on hypotheses to be tested: host, strain, route, endpoints, analysis Protocol development and submission for Duke Institutional Animal Care and Use Committee approval Protocol development and submission for Duke Institutional Biosafety Committee approval BSL2 and BSL3 animal housing (mice, rats, guinea pigs, rabbits, etc.) Microbe acquisition, inoculum preparation, and inoculum validation Registration, acquisition, and inventory for Select Agents (if applicable) Animal acquisition, challenge, health monitoring, euthanasia, and sample collection Administration of test substances Growth of microbe, inoculum preparation, and inoculum validation Administration of challenge dose by the chosen route (aerosol, intranasal, IP, IV, IM, SQ, etc.) Sentinel necropsy to determine dose delivered as appropriate Routine endpoints: Clinical condition, weight, survival, survival time, microbial burden Necropsy with tissue collection Statistical analysis using weight, survival, survival time, and other endpoints as appropriate The Animal Models Shared Resource is integrated with other DHVI Shared Resources: The Aerobiology Shared Resource provides aerosol exposures Microbial burden or host response can be monitored in vivo using the Animal Imaging Shared Resource Samples from experimental animals can be analyzed in the Research Flow Cytometry and Cell Sorting, or the Immune Reconstitution and Biomarker Analysis Shared Resources
Protocols and Documents:
Current Animal Models
Affiliated Centers:
Duke University Center for Translational Research Grant – AI051445 Southeast Regional Center of Excellence for Emerging Infections and Biodefense (SERCEB) - AI057157
Publications:
2006-2008 Yu JS, Peacock JW, Vanleeuwen S, Hsu T, Jacobs WR, Jr., Cayabyab MJ, Letvin NL, Frothingham R, Staats HF, Liao HX, Haynes BF. Generation of mucosal anti-human immunodeficiency virus type 1 T-Cell responses by recombinant Mycobacterium smegmatis. Clin Vaccine Immunol 2006;13:1204-1211. Styer KL, Click EM, Hopkins GW, Frothingham R, Aballay A. Study of the role of CCR5 in a mouse model of intranasal challenge with Y. pestis. Microbes and Infection 2007;9:1135-8 Yu JS, Peacock JW, Jacobs WR Jr, Frothingham R, Letvin NL, Liao HX, Haynes BF. Recombinant bacillus Calmette-Guerin elicits HIV-1 envelope-specific T lymphocytes at mucosal sites. Clin Vaccine Immunol 2007;14:866-93. Davidson EM, Frothingham R, Cook-Deegan R. Science and security: Practical experiences in dual-use review. Science 2007;316:1432-3. Bifani P, Mathema B, Kurepina N, et al (Frothingham R one of 11 authors). The evolution of drug-resistance in Mycobacterium tuberculosis: From a mono-rifampin resistant cluster into increasingly multidrug resistant variants in an HIV sero-positive population. J Infect Dis 2008; 198:90-94. Stout JE, Hopkins GW, McDonald JR, Quinn A, Hamilton CD, Reller LB, Frothingham R. Association between 16S-23S ITS sequence groups of Mycobacterium avium complex and pulmonary disease. J Clin Microbiol 2008; 46:2790-3.