Barney S. Graham, M.D., Ph.D.
Clinical Trials Core Laboratory
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 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 VRC scientific progress, please visit
Selected Publications
Ledgerwood JE, Pierson TC, Hubka SA, Desai N, Rucker S, Gordon IJ, Enama ME, Nelson S, Nason M, Gu W, Bundrant N, Koup RA, Bailer RT, Mascola JR, Nabel GJ, Graham BS; the VRC 303 Study Team. A West Nile Virus DNA Vaccine Utilizing a Modified Promoter Induces Neutralizing Antibody in Younger and Older Healthy Adults in a Phase I Clinical Trial. J Infect Dis. 2011 May;203(10):1396-1404. Epub 2011 Mar 11.
Koup RA, Graham BS, Douek DC. The quest for a T cell immune correlate of protection against HIV: A story of trials and errors [Commentary]. Nature Rev Immunol. 2011; 11:65-70. Epub 2010 Dec 17.
Graham BS, Nabel GJ. Challenges and Prospects for the Development of an HIV Vaccine, in New Generation Vaccines. Fourth edition, Levine MM, Dougan G, Good MF, Liu MA, Nabel GJ, Nataro JP, Rappuoli R, editors. Informa Healthcare, New York, NY, 2010, Chapter 55: pages 585-592.
Graham BS, Walker C. Meeting the Challenge of Vaccine Design to Control HIV and Other Difficult Viruses, in Immunology of Infectious Diseases. Kaufmann SHE, Rouse B, Sacks D, editors. ASM Press, Washington, DC, 2010, Chapter 44: pages 559-570.
Ledgerwood JE, Costner P, Desai N, Holman L, Enama ME, Yamshchikov G, Mulangu S, Hu Z, Andrews CA, Sheets RA, Koup RA, Roederer M, Bailer RT, Mascola JR, Pau MG, Sullivan NJ, Goudsmit J, Nabel GJ, Graham BS, VRC 205 Study Team. A replication defective recombinant Ad5 vaccine expressing ebola virus GP is safe and immunogenic in healthy adults. Vaccine. 2010; 29:304-313. Epub 2010 Oct 27.
Peiperl L, Morgan C, Moodie Z, Li H, Russell N, Graham BS, McElrath MJ, and the NIAID HIV Vaccine Trials Network. Immunization with a single dose of recombinant adenovirus type 5 HIV-1 vaccine induces strong, durable immune responses in persons without pre-existing neutralizing antibodies against the vector (HVTN 054). PLoS ONE. 2010; 5(10):e13579.
Jaoko W, Karita E, Kayitenkore K, Omosa-Manyonyi G, Allen S, Than S, Adams EM, Graham BS, Koup RA, Bailer RT, Smith C, Dally L, Farah B, Anzala O, Muvunyi CM, Bizimana J, Tarragona T, Bergin PJ, Hayes P, Ho M, Loughran K, Komaroff W, Stevens G, Thomson H, Boaz MJ, Cox JH, Schmidt C, Gilmour J, Nabel GJ, Fast P, Bwayo J. Safety and immunogenicity study of multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa. PLoS ONE. 2010 Sep 21; 5(9). pii e12873.
Rosenberg E, Graham BS, Chan E, Bosch R, Stocker V, Maenza J, Markowitz M, Little S, Sax P, Collier A, Nabel GJ, Flynn T, Kuritzkes D, Barouch D, ACTG 5187 study team. Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection. PLoS ONE. 2010: 5(5):e10555.
Koup RA, Roederer M, Lamoreaux L, Fischer J, Novik L, Nason MC, Larkin BD, Enama ME, Martin JE, Bailer RT, Mascola JR, Nabel GJ, Graham BS, and the VRC 009 and VRC 010 Study Teams. Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses. PLoS ONE. 2010; 5(2): e9015.
Freel SA, Lamoreaux L, Chattopadhyay PK, Saunders K, Zarkowsky D, Overman RG, Ochsenbauer C, Edmonds TG, Kappes JC, Cunningham CK, Denny TN, Weinhold KJ , Ferrari G, Haynes BF, Koup RA, Graham BS, Roederer M, Tomaras GD. Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination. J Virol. 2010; 84:4998-5006. Epub 2010 Mar 3.
Kibuuka H, Kimutai R, Maboko L, Sawe F, Schunk MS, Kroidl A, Shaffer D, Eller LA, Kibaya R, Eller MA, Schindler KB, Schuetz A, Millard M, Kroll J, Dally L, Hoelscher M, Bailer R, Cox JH, Marovich M, Birx DL, Graham BS, Michael NL, de Souza MS, Robb ML. A Phase I/II study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus-type 5 boost vaccine in HIV uninfected East Africans (RV 172). J Infect Dis. 2010; 15:600-607.
Graham BS. What does the report of the USMHRP Phase III study in Thailand mean for HIV and for vaccine developers? Clin Exp Immunol. 2009; 158:257-259.
Graham BS, Ledgerwood JE, Nabel GJ. Vaccine development in the 21st century: Changing paradigms for elusive viruses [Commentary]. Clinical Pharmacology and Therapeutics. 2009; 86:234-236.
Ledgerwood JE, Graham BS. DNA vaccines: A safe and efficient platform technology for responding to emerging infectious diseases. Human Vaccines. 2009; 5:623-626.
Martin JE, Graham BS. Vaccination Against Viral Diseases, in “Clinical Virology”, 3rd Edition, Richman DD, Hayden FG, Whitley RJ, editors. ASM Press. Herndon, VA, 2009; Chapter 15: pages 333-349.
Cheng C, Gall JGD, Nason MC, King CR, Koup RA, Roederer M, McElrath MJ, Morgan CA, Baden L, Churchyard G, Keefer MC, Duerr A, Graham BS, Nabel GJ. Differential specificity and immunogenicity of adenovirus 5 neutralizing antibodies elicited by natural infection or immunization. J Virol. 2010; 84:630-638. Epub 2009 Oct 21.
Koup RA, Lamoreaux L, Zarkowsky D, Bailer R, Graham BS, Roederer M. Multiply-deleted replication-defective adenovirus vectors fail to induce measurable vector-specific T cells in human trials. J Virol. 2009; 83:6318-6322. Epub 2009 Apr 1.
Davis KL, Gray ES, Moore PL, Decker JM, Salomon A, Montefiori DC, Graham BS, Keefer MC, Pinter A, Morris L, Hahn BH, Shaw GM. High titer HIV-1 V3-specific antibodies with broad reactivity but low neutralizing potency in acute infection and following vaccination. Virology. 2009; 387:414-426. Epub 2009 Mar 17.
Cecchini S, Negrete A, Virag T, Graham BS, Cohen JI, Kotin RM. Evidence of prior exposure to human bocavirus: A retrospective serological study of 404 adult sera in the United States. Clinical and Vaccine Immunology. 2009; 16:597-604. Epub Feb 25.
Martin JE, Louder MK, Holman LA, Gordon IJ, Enama ME, Larkin BD, Andrews CA, Vogel L, Koup RA, Roederer M, Bailer RT, Gomez PL, Nason M, Mascola JR, Nabel GJ, Graham BS. A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial. Vaccine. 2008; 26:6338-6343. Epub 2008 Sep 26.
Nelson S, Jost CA, Xu Q, Ess J, Martin JE, Oliphant T, Whitehead SS, Durbin AP, Graham BS, Diamond MS, Pierson TC. Maturation of West Nile virus modulates sensitivity to antibody-mediated neutralization. PLoS Pathogens. 2008 May 9; 4(5):e1000060.
Martin JE, Peirson TC, Hubka S, Rucker S, Gordon IJ, Enama ME, Andrews CA, Xu Q, Davis B, Nason M, Fay M, Koup RA, Roederer M, Bailer RT, Gomez PL, Mascola JR, Chang GJ, Nabel GJ, Graham BS. A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults in a phase I clinical trial. J Infect Dis. 2007; 196:1732-1740.
Eller MA, Eller LA, Opollo MS, Ouma BJ, Oballah PO, Galley L, Karnasuta C, Kim SR, Robb ML, Michael N, Kibuuka H, Wabwire-Mangen F, Graham BS, Birx DL, de Souza MS, Cox JH. Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans. Vaccine. 2007; 25:7737-7742. Epub 2007 Sep 17.
Precopio ML, Betts MR, Parrino J, Price DA, Gostick E, Harari A, Pantaleo G, Bailer R, Graham BS, Roederer M, Koup RA. Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8+ T cell responses. J Exp Med. 2007; 204:1405-1416. Epub 2007 May 29.
Catanzaro AT, Roederer M, Koup RA, Bailer RT, Enama ME, Nason MC, Martin JE, Rucker S, Andrews CA, Gomez PL, Mascola JR, Nabel GJ, Graham BS. Phase I clinical evaluation of a six-plasmid multiclade HIV-1 DNA candidate vaccine. Vaccine. 2007; 25:4085-4092. Epub 2007 Mar 7.
Tavel JA, Martin JE, Kelly GG, Enama ME, Shen JM, Gomez PL, Andrews CA, Koup RA, Bailer RT, Stein JA, Roederer M, Nabel GJ, Graham BS. Safety and immunogenicity of a Gag-Pol candidate HIV-1 DNA vaccine administered by a needle-free device in HIV-1 seronegative subjects. Journal of Acquired Immune Deficiency Syndromes. 2007; 44:601-606. Epub 2007 Feb 22.
Parrino J, McCurdy LH, Larkin BD, Gordon IJ, Rucker SE, Enama ME, Koup RA, Roederer M, Bailer RT, Moodie Z, Gu L, Yan L, Graham BS. Safety, immunogenicity and efficacy of modified vaccinia Ankara (MVA) against Dryvax® challenge in vaccinia-naïve and vaccinia-immune individuals. Vaccine 2007; 25:1513-1525. Epub 2006 Nov 7.
Catanzaro AT, Koup RA, Roederer M, Bailer RT, Enama ME, Moodie Z, Gu L, Martin JE, Novik L, Chakrabarti BK, Butman BT, Gall JGD, King CR, Andrews CA, Sheets R, Gomez PL, Mascola JR, Nabel GJ, Graham BS, VRC 006 Study Team. Phase I Safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenoviral vector. J Infect Dis. 2006; 194:1638-1649.
Graham BS, Koup RA, Roederer M, Bailer, Enama ME, Moodie Z, Martin JE, McCluskey MM, Chakrabarti BK, Lamoreaux L, Andrews CA, Gomez PL, Mascola JR, Nabel GJ, VRC 004 Study Team. Phase I safety and immunogenicity evaluation of a multiclade HIV-1 candidate DNA vaccine. J Infect Dis. 2006; 194:1650-1660.
Khurana S, Needham J, Mathieson B, Chavez IR, Catanzaro AT, Bailer RT, Kim J, Polonis V, Cooper DA, Guerin J, Peterson ML, Gurwith M, Nguyen N, Graham BS, Golding H & the HIV Vaccine Trial Network. HIV vaccine trials: A novel assay for differential diagnosis of HIV infections in the face of vaccine-generated antibodies in participants. J Virol. 2006; 80:2092-2099.
Khurana S, Needham J, Park S, Mathieson B, Busch MP, Nemo G, Nyambi P, Zolla-Pazner S, Laal S, Mulenga J, Chomba E, Hunter E, Allen S, McIntyre J, Hewlett I, Lee S, Tang S, Cowan E, Beyrer C, Altfeld M, Yu X, Tounkara A, Koita O, Rodriguez-Chavez IR, Nguyen N, Graham BS, Todd D, Mugenyi P, Ketter N, Fast P, Golding H. HIV-SELECTEST- A novel assay for diagnosis of HIV infections in the face of vaccine generated antibodies: Utility for detection of diverse HIV-1 subtypes. Journal of Acquired Immune Deficiency Syndromes. 2006; 43:304-312.
Martin JE, Sullivan NJ, Enama ME, Gordon IJ, Roederer M, Koup RA, Bailer RT, Chakrabarti BK, Bailey MA, Gomez PL, Andrews CA, Moodie Z, Gu L, Stein JA, Nabel GJ, Graham BS and the VRC 204 Study Team. A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clinical and Vaccine Immunology. 2006; 13:1267-1277. Epub 2006 Sep 20.
Parrino J, Graham BS. Smallpox vaccines: Past, present, and future. J Allergy Clin Immunol. 2006; 118:1320-1326.
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).
Graham BS, Mascola JR. Lessons from failure - Preparing for future HIV vaccine efficacy trials. J Infect Dis. 2005; 191:647-649.
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.
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.
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.
Graham BS. Clinical Trials of HIV Vaccines. Ann Rev Med. 2002; 53:207-221.
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, 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, 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.
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, 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, 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, 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, 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, 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.
Montefiori DC, Graham BS, Zhou JT, Zhou JY, Bucco R, Schwartz DH, Cavacini LA, Posner MR, 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, 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, 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.
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, 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.
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, 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, Karzon DT. Development of an AIDS vaccine: Biological and ethical challenges. Infect Dis Clin N Am. 1990; 4(2):223-243.
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
Current Clinical Studies
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