CoresInvestigators
Haynes W. Sheppard
Director
Virology and Immunology Core
Specialty: Immunology and Virology of HIV
Undergraduate Education: UC San Diego
Graduate School: UC Irvine
Post Doc: NIH Laboratory of Parasitic Disease
Dr. Sheppard has had a long-term interest in both HIV/AIDS vaccines and the immunology, natural history, and pathogenesis of HIV infection, including 10 years as a "key investigator" for the San Francisco Men's Health Study (SFMHS) cohort, 5 years as the Principal Investigator for the HIVNET Central Laboratory (1994-1999), and currently the PI of the International Coordinating Laboratory of the HIV Vaccine Trials Network (HVTN).
As PI of the primary laboratory for the SFMHS, Dr. Sheppard has directed extensive studies of both the virology and immunology of HIV infection and their association with the rate of disease progression. These studies emphasized the initial immune response to HIV, virus load, virus strain variation, coreceptor polymorphism, and the adverse consequences of nonspecific immune system activation. A model of HIV pathogenesis was developed in which CD4-mediated signals, nonspecific immune system activation, and programmed cell death are the primary determinants of immune system destruction.
As PI of an HIV vaccine trials Central Laboratory (HCL) Dr. Sheppard also served a member of the Scientific Steering Committee of HIVNET and is currently a member of the Laboratory Science Committee of the HVTN. Under Dr. Sheppard's leadership, the HCL has maintained CLIA-certification as a clinical diagnostic laboratory, and has provided both standardized trial support and ancillary studies in areas of; Standard and cross-clade CTL assays, neutralizing antibody assays, diagnostic serology and binding antibody assays, "detuned" serology, diagnostic PCR (RNA and DNA), RNA/DNA quantitation, virus isolation and phenotyping, HMA/HTA (subtyping and tracking of transmission), DNA sequencing, T cell proliferation, CD8 virus suppression (chemokines and CAF), coreceptor genetics, cytokine assays, flow cytometry, SCIDhu mice (including transplants with vaccinee cells). The HCL has also been responsible for coordinating Quality Assurance activities and training for a network of international laboratories, which provide local support for vaccine trials.
In addition to providing this laboratory support for testing HIV vaccine candidates, Dr. Sheppard has recently initiated preclinical development of an HIV vaccine candidate based on a whole inactivated virion concept but using novel methods to preserve native envelope protein structure.
Selected Publications: Ascher MS and Sheppard HW. AIDS as immune system activation: a model for pathogenesis. Clin. Exp. Immunol. 1988; 73:165-167.
Sheppard HW, Ascher MS, McRae B, Anderson RE, Lang W, Allain JP. The initial immune response to HIV and immune system activation determine the outcome of HIV disease. J.A.I.D.S. 1991; 4:704-12.
Sheppard HW and Ascher MS. The relationship between AIDS and immunologic tolerance. J.A.I.D.S. 1992; 5:143-147.
Sheppard HW and Ascher MS. The natural history and pathogenesis of HIV infection. Chapter in Annual Reviews of Microbiology, 1992; 46:533-564.
Sheppard HW, Ascher MS, Winkelstein W, Vittinghoff E, Moss A, Osmond D, Shibosky. The use of T lymphocyte subset enumeration in the case definition for AIDS. J.A.I.D.S. 1993, 6:287-294.
Sheppard HW, Lang W, Ascher MS, Vittinghoff E, Winkelstein W. The characterization of non-progressors: Long-term HIV-1 infection with stable CD4+ T-cell levels. AIDS 1993, 7:1159-1166.
Wilson SE, Pederson SL, Kunich JC, Wilkins VL, Mann DL, Mazzara GP, Tartaclia J, Celum CL, and Sheppard HW. Cross-clade envelope glycoprotein 160-specific CD8+ cytotoxic T lymphocyte responses in early HIV type-1 clade-B infection. AIDS Res Hum Retroviruses 1998; 14:925-937.
Lole KS Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, and Ray SC. Full-length Human Immunodeficiency Virus type-1 genomes from subtype C-infected seroconverters in India, with evidence of inter-subtype recombination. J Virol. 1999; 73:152-160.
Celum C, Buchbinder S, Donnell D, Douglas JM, Mayer K, Koblin B, Marmor M, Bozeman S, Grant RM, Flores J, and Sheppard HW. Early Human Immunodeficiency Virus (HIV) infection in the HIV Network for Prevention Trials Vaccine Preparedness Cohort: Risk Behaviors, Symptoms, and Early Plasma and Genital Tract Virus Load. JID 2001, 183:23-35.
Marmor. M., Shepperd HW, Donnell D, Bozeman S, Celum C, Buchbinder S, Koblin B, Seage III GR. Homoaygous and Heterosygous CCR5-D32 Genotypes are Associated With Resistance to HIV Infection. JAIDS 2001, 27:472-481.