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Vaccine Research Center (VRC)

Srinivas S. Rao D.V.M., Ph.D, M.B.A., Diplomate, ACVP

Biodefense Vaccine Translational Research and Licensure Program/Laboratory Animal Medicine

Description of Progam

The BVRP/LAM provides all aspects of oversight and programmatic assistance to support teaching, training and research involving laboratory animals as well as efficacy studies in support of the goals of the Biodefense Research Section (BRS). The program also oversees animal facilities that are fully AAALAC accredited, ensuring adherence to all Federal regulations as published in the Animal Welfare Act (AWA): (a) Guide for the Care and Use of Laboratory Animals (Guide), (b) Public Health Service Policy, (c) the U.S. Government Principles Regarding the Care and Use of Animals, and (d) NIH Manual 3040-2. In addition to the oversight of efficacy studies, Dr. Rao participates in support of VRC-Biodefense products in the conduct of animal studies, preclinical safety, contract management, and Good Laboratory Practices (GLP) compliance for BSL-2, 3, and 4 reagents as essential. Dr. Rao coordinates the use of laboratory animals with the policies of the NIH including the Office of Animal Care and Use (OACU), and serves as the attending veterinarian on the Animal Care Use Committee (ACUC).

The division is unique among the various Institutes and Centers at the NIH in its support of in vivo research at the VRC. We are committed to the pursuit and achievement of scientific excellence by providing the highest quality in vivo research support and service, as well as providing judicious and humane use of animals in VRC research. The VRC’s entire in vivo program is centralized in the program’s services and support of pre-clinical studies. Furthermore, the program also pursues independent and collaborative research projects related to vaccine development in animal models for infectious disease such as Ebola, Avian Influenza and HIV.

  1. In vivo research support and service

    The BVRP/LAM provides support and service for in vivo research conducted by the VRC, managing all preclinical safety and regulatory issues. It is the VRC’s primary resource for consultation, collaboration, and professional assistance for in vivo research, including animal model development for many species such as mouse, guinea pig, chickens, ferrets, rabbits, and non-human primates. The program specializes in the development and review process of the Animal Care and Use protocols, and ensures that all animal study protocols adhere to ACUC policies and GLP. The program also offers assistance with establishing contracts for services that cannot be provided in the Building 40 vivarium. Such contracts may be required for species such as chickens, rabbits, ferrets, and non-human primates, or for special conditions such as a BSL3 facility.

  2. Lab Animal Facility

    In addition to providing animal supplies through the establishment of contracts with other facilities, the BVRP/LAM also serves as a fully functioning, AAALAC accredited, animal research facility which provides quality animal husbandry services, veterinary care, and facility management support for mice, rats, and guinea pigs. In addition, the facility has expanded the non-human primate program by 50% in the last year. Preventative medical care, routine surveillance, and quality assurance are all provided for vendor- and colony-produced animals. In addition, mouse breeding colonies may be established and maintained upon the investigator’s request.

    A variety of technical services are also performed by facility staff, such as: parenteral injections or oral administration of ACUC-approved experimental materials, blood, tissue, and serum collection, surgical manipulations, animal identification procedures, electroporation procedures, anesthesia/analgesic administration, and other procedures as needed. The Veterinary Care Unit also offers training, free of charge, for those who wish to perform these procedures themselves.

  3. Collaborative Research Projects

    In recent years, BVRP/LAM has also become heavily involved in numerous collaborative research projects ranging from topics such as highly pathogenic avian influenza, HIV/AIDS, and novel vaccine delivery methods to veterinary pathology reports and anesthesia evaluation. The program specializes in immunohistochemistry, in situ hybridization, and pathology analysis, and has contributed to numerous publications include the following:

    • Multivalent DNA vaccine for Avian Influenza in poultry (PLoS One)
    • Development of Aerosol Vaccination (submitted, Nature)
    • Clinical reports for Pathology (Veterinary Pathology) and Anesthesia in Guinea pigs (J Am Assoc Lab Anim Sci)
    • Measles- SIV co-infection study (J of Immunology)
    • Respiratory Syncytial Virus animal model and pathology (submitted, J of Virology)

Selected Publications

Rao SS, Styles D, Kong W, Andrews C, Gorres JP, Nabel GJ. A Gene-Based Avian Influenza Vaccine in Poultry. *accepted for publication in Poultry Science

Rao SS, Bryant M, Herbert R, Sullivan N, Murray C, Bacher J, Safdar N. Idiopathic Chondrolysis Condition in Two Young, Wild-caught Cynomolgus Monkeys (Macaca fascicularis) Reared in Captivity. *accepted for publication in May/June 2009 issue of Veterinary Pathology

Dang V, Bao S, Ault A, Murray C, McFarlane-Mills J, Chiedi C, Dillon M, Todd JP, Detolla L, Rao S. Efficacy and safety of five injectable anesthetic regimens for chronic blood collection from the anterior vena cava of Guinea pigs. J Am Assoc Lab Anim Sci. 2008 Nov;47(6):56-60.

Permar SR, Kang HH, Carville A, Mansfield KG, Gelman RS, Rao SS, Whitney JB, Letvin NL. Potent simian immunodeficiency virus-specific cellular immune responses in the breast milk of simian immunodeficiency virus-infected, lactating rhesus monkeys. J Immunol. 2008 Sep 1;181(5):3643-50.

Rao SS, Kong WP, Wei CJ, Yang ZY, Nason M, Styles D, DeTolla LJ, Sorrell EM, Song H, Wan H, Ramirez-Nieto GC, Perez D, Nabel GJ. Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza in Chickens and Mice. PLoS One. 2008 Jun; 3(6): e2432

Permar SR, Rao SS, Sun Yue, Bao S, Buzby AP, Kang HH, Letvin NL. Clinical Measles after Virus Challenge in Simian Immunodeficiency Virus-Infected Measles Virus-Vaccinated Rhesus Monkeys. The Journal of Infectious Diseases. 2007; 196:1784-1793

Letvin NL, Rao SS, Dang V, Buzby AP, Korioth-Schmitz B, Dombagoda D, Parvani JG, Clarke RH, Bar L, Carlson KR, Kozlowski PA, Hirsch VM, Mascola JR, Nabel GJ. No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys. J Virol. 2007 Nov;81(22):12368-74. Epub 2007 Aug 8.

Shu Y, Winfrey S, Yang ZY, Xu L, Rao SS, Srivastava I, Barnett SW, Nabel GJ, Mascola JR. Efficient protein boosting after plasmid DNA or recombinant adenovirus immunization with HIV-1 vaccine constructs. Vaccine. 2007 Feb.; 25(8): 1398-408.

Srinivas S. Rao, Phillip Gomez, John R. Mascola, Vi Dang ,Georgia R. Krivulka, Faye Yu, Carol I. Lord, Ling Shen, Robert Bailer, Gary J. Nabel, Norman L. Letvin. Comparative Evaluation of Three Different Intramuscular Delivery Methods for DNA Immunization in a Nonhuman Primate Animal Model. Vaccine. 2006 Jan.; 24(3):367-73.

Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006 Dec.; 12(12):1365-1371.

Sun Y, Schmitz JE, Buzby AP, Barker BR, Rao SS, Xu L, Yang ZY, Mascola JR, Nabel GJ, Letvin NL. Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge. J Virol. 2006 Nov.; 80(22): 10950-6.

Liu X, Lagenaur LA, Simpson DA, Essenmacher KP, Frazier-Parker CL, Liu Y, Tsai D, Rao SS, Hamer DH, Parks TP, Lee PP, Xu Q. Engineered vaginal lactobacillus strain for mucosal delivery of the human immunodeficiency virus inhibitor cyanovirin-N. Antimicrob Agents Chemother. 2006 Oct.; 50(10):3250-9.

Letvin NL, Mascola JR, Sun Y, Gorgone DA, Buzby AP, Xu L, Yang ZY, Chakrabarti B, Rao SS, Schmitz JE, Montefiori DC, Barker BR, Bookstein FL, Nabel GJ. Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science. 2006 Jun.; 312(5779):1530-3.

Rao S, Hu S, McHugh L, Lueders K, Henry K, Zhao Q, Fekete RA, Kar S, Adhya S, Hamer DH. Toward a live microbial microbicide for HIV: commensal bacteria secreting an HIV fusion inhibitor peptide. Proc Natl Acad Sci USA. 2005 Aug.; 102(34):11993-8.

Smith JM, Rao SS, Stump KC, Benazzi C, Sarli G, DeTolla LJ. Mammary ductal carcinoma with comedo pattern in a rhesus macaque. Contemp Top Lab Anim Sci. 2005 Jul.; 44(4): 29-33.

Jeffrey D. Hasday, Allen Garrison, Ishwar S. Singh, Theodore Standiford, Garrettson S. Ellis, Srinivas Rao, Ju-Ren He, Penny Rice, Mariah Frank, Simeon E. Goldblum, and Rose M. Viscardi. Febrile-Range Hyperthermia Augments Pulmonary Neutrophil Recruitment and Amplifies Pulmonary Oxygen Toxicity. Am J Pathol. 2003 Jun;162(6):2005-17.

Viscardi RM, Kaplan J, Lovchik JC, He JR, Hester L, Rao S, Hasday JD. Characterization of a murine model of Ureaplasma urealyticum pneumonia. Infect Immun. 2002 Oct; 70(10):5721-9.

Vigneulle RM, Rao S, Fasano A, MacVittie TJ. Structural and functional alterations of the gastrointestinal tract following radiation-induced injury in the rhesus monkey. Dig Dis Sci. 2002 Jul;47(7):1480-91.

Reid W, Sadowska M, Denaro F, Rao S, Foulke J Jr, Hayes N, Jones O, Doodnauth D, Davis H, Sill A, O'Driscoll P, Huso D, Fouts T, Lewis G, Hill M, Kamin-Lewis R, Wei C, Ray P, Gallo RC, Reitz M, Bryant J. An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci USA. 2001 Jul 31;98(16):9271-6.

Reid WC, Carmichael KP, Srinivas S, Bryant JL. Pathologic changes associated with use of tribromoethanol (avertin) in the Sprague Dawley rat. Lab Anim Sci. 1999 Dec;49(6):665-7. No abstract available.

Bunnell JE, Trigiani ER, Srinivas SR, Dumler JS. Development and distribution of pathologic lesions are related to immune status and tissue deposition of human granulocytic ehrlichiosis agent-infected cells in a murine model system. J Infect Dis. 1999 Aug;180(2):546-50.

Navarro-Garcia F, Eslava C, Villaseca JM, Lopez-Revilla R, Czeczulin JR, Srinivas S, Nataro JP, Cravioto A. In vitro effects of a high-molecular-weight heat-labile enterotoxin from enteroaggregative Escherichia coli. Infect Immun. 1998 Jul;66(7):3149-54.

Elliott SJ, Srinivas S, Albert MJ, Alam K, Robins-Browne RM, Gunzburg ST, Mee BJ, Chang BJ. Characterization of the roles of hemolysin and other toxins in enteropathy caused by alpha-hemolytic Escherichia coli linked to human diarrhea. Infect Immun. 1998 May;66(5):2040-51.

Xu M, Kumar D, Srinivas S, Detolla LJ, Yu SF, Stass SA, Mixson AJ. Parenteral gene therapy with p53 inhibits human breast tumors in vivo through a bystander mechanism without evidence of toxicity. Hum Gene Ther. 1997 Jan 20;8(2):177-85.

DeTolla LJ, Srinivas S, Whitaker BR, Andrews C, Hecker B, Kane AS, Reimschuessel R. Guidelines for the Care and Use of Fish in Research. ILAR J. 1995;37(4):159-173. No abstract available.

Note: Srinivas S. Rao was previously S. Srinivas

Laboratory Animal Medicine (LAM) Program
Left to Right: Alyse Zajac (Research Specialist), Carmelo Chiedi (Facility Manager), Jumagal Noor (Research Specialist), Srinivas Rao (Animal Program Director), Linda Bessacque (Administrative Assistant), John-Paul Todd (Research Associate), Saran Bao (Research Associate), Alida Ault (APC), J. Patrick Gorres (Post-baccalaureate IRTA)

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Srinivas S. Rao D.V.M., Ph.D, M.B.A., Diplomate, ACVP  

Contact Info

Srinivas S. Rao D.V.M., Ph.D, M.B.A., Diplomate, ACVP, Chief, Laboratory of Animal Medicine
Phone: 301-594-8465
E-mail: srao1@mail.nih.gov
Mail:
NIH
Vaccine Research Center
40 Convent Drive
Rm. 1407
Bethesda, MD 20892-3015

See Also

  • Vaccine Research Center
  • VRC Research Areas

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    Srinivas S. Rao D.V.M., Ph.D, M.B.A., Diplomate, ACVP  

    Contact Info

    Srinivas S. Rao D.V.M., Ph.D, M.B.A., Diplomate, ACVP, Chief, Laboratory of Animal Medicine
    Phone: 301-594-8465
    E-mail: srao1@mail.nih.gov
    Mail:
    NIH
    Vaccine Research Center
    40 Convent Drive
    Rm. 1407
    Bethesda, MD 20892-3015

    See Also

  • Vaccine Research Center
  • VRC Research Areas