Barney S. Graham, M.D., Ph.D.
Description of Research Program
The primary mission of the VRC Clinical Trials Core (CTC) is to evaluate candidate HIV vaccines in Phase I clinical trials. A secondary mission is to evaluate candidate vaccines for biodefense and emerging infectious diseases. The goals of the CTC are to:
- Advance promising vaccine candidates into human trials
- Optimize volunteer safety, confidentiality, knowledge, and convenience
- Maintain Good Clinical Practice standards exceeding requirements mandated in 21 CFR part 11, including compliance with all regulatory agencies and committees as outlined in 45 CFR part 46
- Design protocols that achieve clinical development objectives in a scientifically rigorous and time efficient manner
- Organize the operational aspects of clinical protocols to optimize volunteer safety and minimize length of study
- Collect and maintain high quality clinical data
- Collect and distribute high quality clinical samples
- Collect demographic, behavioral, and marketing data to inform recruitment efforts
- Perform integrated analyses of clinical and immunological data, and prepare clinical trial data for presentation and publication
- Provide community education and support to local organizations
- Provide guidance and assistance to other groups involved in vaccine evaluation
- Interface internally with VRC production, regulatory, administrative, and laboratory groups, and externally with extramural NIAID, clinical trial networks, regulatory agencies, international organizations, and industry partners to achieve efficient transitions through each stage of the clinical development process
- Train physician-scientists in the science of vaccinology
- Conduct clinical trials of therapeutic immunization using preventive vaccine candidates.
The VRC CTC is organized into three major sections: 1) protocol development and management, 2) recruitment and outreach, and 3) clinical operations. The sections are interdependent and work in harmony to accomplish all the tasks required to complete the clinical trials. The CTC performs Phase I studies of candidate vaccines and also conducts natural history studies, and clinical screening protocols that help support basic research efforts and other needs of the Immunology laboratories.
Advanced product development and larger clinical trials require partnership with extramural clinical trial networks and industry. The CTC is very involved in the development and maintenance of relationships with these critical partners and plays an important role in the preparation, conduct, oversight, and interpretation of extramural clinical trials.
For updates on the VRC’s scientific progress, please visit:
Selected Publications
Graham BS, Karzon DT. Development of an AIDS vaccine: Biological and ethical challenges. Infect Dis Clin N Am 1990; 4(2):223-243.
Dolin R, Graham BS, Greenberg SB, Tackett CO, Belshe RB, Midthun K, Clements ML, Gorse GJ, Horgan BW, Atmar RL, Karzon DT, Bonnez W, Fernie BF, Montefiori DC, Stablein DM, Smith GE, Koff WC, and the NIAID AIDS Vaccine Clinical Trials Network: Safety and immunogenicity of an HIV-1 recombinant gp160 candidate vaccine in humans. Ann Intern Med 1991; 114:119-127.
Graham BS, Belshe RB, Clements ML, Dolin R, Corey L, Wright PF, Gorse GJ, Midthun K, Keefer MC, Roberts NJ, Jr, Schwartz DH, Agosti JM, Fernie BF, Stablein DM, Montefiori DC, Lambert JS, Hu S-L, Esterlitz JR, Lawrence D, Koff WC, and the AIDS Vaccine Clinical Trials Network. Vaccination of vaccinia-naive adults with HIV-1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. J Infect Dis 1992; 166:244-252.
Graham BS, Matthews TJ, Belshe RB, Clements ML, Dolin R, Wright PF, Gorse GJ, Schwartz DH, Keefer MC, Bolognesi DP, Corey L, Stablein DM, Esterlitz JR, Hu S-L, Smith G, Fast P, Koff WC, and the AIDS Vaccine Clinical Trials Network. Augmentation of human immunodeficiency virus type 1 neutralizing antibody by priming with gp160 recombinant vaccinia and boosting with rgp160 in vaccinia-naive adults. J Infect Dis 1993; 167:533-537.
Montefiori DC, Graham BS, Zhou JT, Zhou JY, Bucco R, Schwartz DH, Cavacini LA, Posner MR, and the NIH-NIAID AIDS Vaccine Clinical Trials Network. V3-specific neutralizing antibodies in sera from HIV-1 gp160-immunized volunteers block virus fusion and act synergistically with human monoclonal antibody to the conformation-dependent CD4 binding site of gp120. J Clin Invest 1993; 92:840-847. Accompanying editorial: Schooley RT. Just (don't) do it. JCI 1993; 92:535.
Graham BS, Gorse GJ, Schwartz DH, Keefer MC, McElrath J, Matthews TJ, Wright PF, Belshe RB, Clements ML, Dolin R, Corey L, Bolognesi DP, Stablein DM, Esterlitz JR, Hu S-L, Smith G, and the AIDS Vaccine Clinical Trials Network. Determinants of antibody response after rgp160 boosting in vaccinia-naive volunteers primed with gp160 recombinant vaccinia. J Infect Dis 1994; 170:782-786.
Graham BS, Wright PF. Candidate AIDS Vaccines. N Engl J Med 1995; 333:1331-1339.
Mascola JR, Snyder SW, Weislow OS, Belay SM, Belshe RB, Schwartz DH, Clements ML, Dolin R, Graham BS, Gorse GJ, Keefer MC, McElrath MJ, Walker MC, Wagner KF, McNeil JG, McCutchan FE, Burke DS, and the AIDS Vaccine Evaluation Group. Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. J Infect Dis 1996; 173:340-348.
Graham BS, Keefer MC, McElrath J, Gorse GJ, Schwartz DH, Belshe RB, Clements ML, Dolin R, Corey L, Wright PF, Sposto R, Stablein DM, Chernoff D, Dekker C, and the AIDS Vaccine Clinical Trials Network. Safety and immunogenicity of a candidate HIV-1 vaccine in healthy adults: Recombinant envelope glycoprotein gp120. Ann Intern Med 1996; 125:270-279.
Graham BS, McElrath MJ, Connor RI, Schwartz DH, Gorse GJ, Keefer MC, Mulligan MJ, Matthews TJ, Wolinsky SM, Montefiori DC, Vermund SH, Lambert JS, Corey L, Belshe RB, Dolin R, Wright PF, Korber BT, Wolff MC, Fast PE, and the AIDS Vaccine Evaluation Group. Analysis of intercurrent HIV-1 infections in Phase I and II trials of candidate AIDS vaccines. J Infect Dis 1998; 177:310-319.
Connor RI, Korber BTM, Graham BS, Hahn BH, Ho DD, Walker BD, Neumans A, Vermund S, Mestecky J, Jackson S, Cao Y, Gao F, Kalams S, Kuntsman K, McDonald D, Fenamore E, McWilliams N, Morrison S, Trkola A, Moore JP, Wolinsky SM. Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J Virol 1998; 72:1552-1576.
Graham BS. Clinical Trials of HIV Vaccines. Ann Rev Med 2002; 53:207-221.
Womack CA, Liu M, Graham BS. Challenges and Current Progress in the Development of HIV/AIDS Vaccines, in New Generation Vaccines. Third Edition, Levine MM, Kaper JB, Rappuoli R, Liu M, Good M, editors. Marcel Dekker, Inc., New York, NY, 2003, pages 573-581.
Lee D, Graham BS, Chiu YL, Gilbert P, McElrath MJ, Belshe R, Buchbinder S, Sheppard HW, Koblin B, Mayer K, Keefer M, Mulligan M, Celum C. Breakthrough infections during Phase I-II prime-boost HIV vaccine trials with canarypox vectors (ALVACTM) and recombinant gp120 or gp160. J Infect Dis 2004; 190:903-907.
McCurdy LH, Larkin BD, Martin JE, Graham BS. Modified vaccinia virus Ankara: Potential as an alternative smallpox vaccine. Clin Infect Dis 2004; 38:1749-1753.
Graham BS, Mascola JR. Lessons from failure - Preparing for future HIV vaccine efficacy trials. J Infect Dis 2005; 191:647-649.
Catanzaro AT, Graham BS. Rationale for Current HIV Vaccine Clinical Trials, in "Recent Advances in HIV Infection Research". Gualberto Buela-Casal and María Paz Bermúdez, editors, University of Granada. Spain. 2005, (in press).
If you are interested in a Research Fellowship, please send your CV to:
Barney S. Graham, M.D., Ph.D.
NIH/Vaccine Research Center
Building 40, Room 2502
40 Convent Drive, MSC 3017
Bethesda, MD 20892-3017
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