Scientific Overview

Basic and Clinical Development of Vaccines and Other Prevention Strategies
against HIV-1
HIV pathogenesis and treatment had been the major areas of study in the past. Since 2001, my laboratory has focused on development of novel vaccines against HIV-1, both in the laboratory and in the clinic. Our first two candidate vaccines were ADVAX, a DNA-based multigenic clade C/B’ DNA-based vaccine, and ADMVA, a multigenic clade C/B’ vaccine utilizing the Modified Vaccinia Ankara virus. These vaccines have completed Phase I clinical testing. In particular, we have explored the delivery of ADVAX using an in vivo electroporation device. We are also developing novel vaccines with improved cellular and humoral immunogenicity by targeting dendritic cells, a project funded by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery.

Our group is now actively designing vaccine constructs that attempt to raise neutralizing antibodies directed to the viral envelope glycoproteins. We are also developing vaccine platform technologies that try to target our immunogens to dendritic cells. Specifically, we are utilizing Fc-fusion and flagellin-fusion approaches to deliver the antigen of interest to dendritic cells via activation Fc receptors and TLR5, respectively.

Another strategy to HIV prevention is to test monoclonal antibodies directed to domain-2 of CD4, the primary receptor for HIV on the surface of target cells. We are now examing an antibody known as ibalizumab to assess its ability to protect against SIV in monkeys and HIV in humans. We are also endeavoring to develop variants of ibalizumab that have improved affinity, pharmacokinetics, and efficacy. Furthermore, we are exploring the use of AAV vector to express this monoclonal antibody to block SIV/HIV transmission. Click here for more information on Ho Ibalizumab Development Consortium.

Our group is also making "fusion" antibody constructs that have multiple antibody variable domains, each of which is capable of blocking a step or a site involved in HIV entry. These biologics could be used for both prophylaxis and treatment.

Our laboratory works to brighten the design and delivery of HIV vaccines to heighten the body’s immune response to these vaccines. One strategy involves designing vaccines to “target” dendritic cells, a specialized immune cell in the body that coordinates many aspects of the immune response. Studies have shown that vaccines targeting dendritic cells elicit a longer and stronger immune response. This work is being sponsored by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery, and is being conducted with a consortium of scientists. Another strategy involves antibodies that could block HIV infection by interfering with the binding to CD4, the receptor for HIV. Our group is also pursuing the use of a monoclonal antibody, known as ibalizumab, in preventing SIV infection in monkeys and HIV infection in humans. Moreover, we are creating novel forms of HIV-inhibitory antibodies that could be used for both prophylaxis and treatment.

Please click here to be directed to the China AIDS Initiative website

NAME: David D. Ho, M.D.

TITLE: Director, CEO and Professor

ADDRESS:

Scientific Director, CEO & Irene Diamond Professor Aaron Diamond AIDS Research Center The Rockefeller University 455 First Avenue New York, NY 10016

TELEPHONE: (212) 448-5100

TELEFAX: (212) 725-1126

EDUCATION

1970-1971	Massachusetts Institute of Technology
1971-1974	California Institute of Technology (B.S.)
1974-1978	Harvard Medical School (M.D.)

INTERNSHIP AND RESIDENCY

1978-1981	Resident in Internal Medicine Cedars-Sinai Medical Center, UCLA School of Medicine
1981-1982	Chief Medical Resident Cedars-Sinai Medical Center, UCLA School of Medicine

FELLOWSHIP

1982-1985

Clinical and Research Fellow in Medicine Massachusetts General Hospital and Harvard Medical School

ACADEMIC APPOINTMENTS

1985-1986	Instructor in Medicine Massachusetts General Hospital and Harvard Medical School
1986-1990	Physician and Research Scientist Cedars-Sinai Medical Center
1986-1989	Assistant Professor of Medicine in Residence UCLA School of Medicine
1989-1990	Associate Professor of Medicine in Residence UCLA School of Medicine
1990-1996	Professor of Medicine and Microbiology, NYU School of Medicine
1996-present	Professor and Physician, The Rockefeller University
1990-present	Scientific Director and Chief Executive Officer Aaron Diamond AIDS Research Center
2007-present	Director & Professor, Comprehensive AIDS Research Center, Tsinghua University

LICENSURE AND CERTIFICATION

1978	Licensure, State of California
1982	Licensure, Commonwealth of Massachusetts
1982	Certification, American Board of Internal Medicine
1990	Licensure, State of New York

HONORARY DOCTORATES:

1997	Bard College
1998	Graduate School of CUNY
1998	Swarthmore College
1999	Tufts University
1999	SUNY
2000	Columbia University
2001	University of Natal
2005	Tulane University
2006	Bates College
2006
2008	National Yang-Ming University
2008
	Read more...

Commencement Speeches

1997	Harvard-MIT Health Sciences & Technology
1997	California Institute of Technology
1998
2000	Harvard School of Public Health
2005	Tulane University

Election to Academies:

1997	American Academy of Arts and Sciences
1997	Institute of Medicine, National Academy of Sciences
1998	Academia Sinica, Republic of China
2004	Chinese Academy of Engineering

SELECT AWARDS AND HONORS

1991	Ernst Jung-Preis Fur Medizin 1991 (Ernst Jung Price in Medicine 1991, Germany)
1993	Mayor’s (NY) Award for Excellence in Science and Technology
1996	Squibb Award, Infectious Diseases Society of America
1997	Bernard Fields Memorial Award
1999	Hoechst Marion Roussel Award (now Aventis Award)
2001	Irene Diamond Professorship, The Rockefeller University
2003	Lewis and Jack Rudin New York Prize for Medical Research
2006
	Read More...

Special Recognitions:

1996
	Time Magazine Man of the Year 1996
	Time Magazine Interview
	Play video
2001

COMMITTEE ASSIGNMENTS & BOARD MEMBERSHIPS

1997-2007	Board of Trustees, California Institute of Technology
1998-Present	Board of Directors, Aaron Diamond AIDS Research Center
1998-2004	Board of Overseers, Harvard University
2003-Present	Board member, MIT Corporation

• Ho DD, Schooley RT, Rota TR, Kaplan JC, Salahuddin SZ, Gonda MA, Hirsch MS. HTLV-III in semen and blood of a healthy homosexual man. Science 1984; 226:451-453. [view]
• Ho DD, Rota TR, Schooley RT, Kaplan JC, Allan JD, Groopman JE, Resnick L, Felsenstein D, Andrews CA, Hirsch MS. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N. Engl. J. Med. 1985; 313:1493-1497.[view]
• Ho DD, Moudgil T, Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N. Engl. J. Med. 1989; 321:1621-1625.[view]
• Daar ES, Moudgil T, Meyer RD, Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N. Engl. J. Med. 1991; 324:961-964. [view]
• Zhu T, Mo H, Wang N, Nam DS, Cao Y, Koup R, Ho DD. Genotypic and phenotypic characterization of HIV-1 in patients with primary infection. Science 1993; 261:1179-81. [view]
• Cao Y, Qin L, Zhang GL, Safrit J, Ho DD. Virologic and immunologic characterization of long-term survivors of HIV-1 infections. N. Engl. J. Med. 1995; 332:201-8. [view]
• Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virion and CD4 lymphocytes in HIV-1 infection. Nature 1995; 373:123-6. [view]
• Markowitz M, Saag M, Powderly W, Hurley AM, Hsu A, Valdes JM, Henry D, Sattler F, La Marca A, Leonard JM, Ho DD. A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N. Engl. J. Med. 1995; 333:1534-9. [view]
• Ho DD. Time to hit HIV, early and hard. N. Engl. J. Med. 1995; 333:450-1. [view]
• Spira AI, Marx PA, Patterson BK, Mahoney J, Koup RA, Wolinsky SM, Ho DD. Cellular targets of infection and route of viral dissemination following intravaginal inoculation of SIV into rhesus macaques. J. Exp. Med. 1996; 183:215-25. [view]
• Perelson AS, Neumann AU, Markowitz M, Leonard J, Ho DD. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 1996; 271:1582-6. [view]
• Ho DD. Viral counts count in HIV infection. Science 1996; 272:1124-5. [view]
• Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, Kunstman K, Erickson D, Dragon E, Landau N, Phair J, Ho DD, Koup RA. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nature Med. 1996; 2:1240-3. [view]
• Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, Markowitz M, Ho DD. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 1997; 387:188-91. [view]
• Zhu T, Korber BT, Nahmias AJ, Hooper E, Sharp PM, Ho DD. An African HIV-1 sequence from 1959 and implications for the origin of the epidemic. Nature 1998; 391:594-7. [view]
• Mohri H, Bonhoeffer S, Monard S, Perelson AS, Ho DD. Rapid turnover of T lymphocytes in SIV-infected rhesus macaques. Science 1998; 279:1223-7. [view]
• Ho DD. Toward HIV eradication or remission: the tacks ahead. Science 1998; 280:1866-7. [view]
• Zhang L, Ramratnam B, Tenner-Racz, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. Quantifying residual HIV-1 replication in patients receiving effective combination antiretroviral therapy. N. Engl. J. Med. 1999; 340:1605-13. [view]
• Jin X, Bauer DE, Tuttleton SE, Lewin S, Gettie A, Kostrikis L, Blanchard J, Irwin CE, Safrit JT, Zhang L, Ho DD. Dramatic rise in plasma viremia after CD8+ T-cell depletion in simian immunodeficiency virus-infected macaques. J. Exp. Med. 1999; 189:991-8. [view]
• Ramratnam B, Bonhoeffer S, Binley J, Hurley A, Zhang L, Mittler, Markowitz M, Moore JP, Perelson AS, Ho DD. Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis. Lancet 1999; 354:1782-5. [view]
• Zhang L, Lewin S, Markowitz M, Lin H-H, Skulsky E, Karanicolas R, He Y, Jin X, Tuttleton S, Vesanen M, Spiegel H, Kost R, J. van Lunzen, H-J. Stellbrink, Wolinsky S, Borkowsky W, Palumbo P, Kostrikis LG, Ho DD. Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J. Exp. Med. 1999; 190:725-32. [view]
• Ramratnam B, Mittler JE, Zhang L, Boden D, Hurley A, Fang F, Macken CA, Perelson AS, Markowitz M, Ho DD. The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged antiretroviral therapy. Nature Med. 2000; 6:82-5. [view]
• Mohri H, Perelson AS, Tung K, Ribeiro R, Ramratnam B, Markowitz M, Kost R, Hurley A, Weinberger L, Cesar D, Hellerstein MK, Ho DD. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J. Exp. Med. 2001; 194:1277-87. [view]
• Ho DD and Huang Y. The HIV-1 vaccine race. Cell. 2002; 110:135-8. [view]
• Linqi Zhang, Wenjie Yu, Tian He, Jian Yu, Rebecca E. Caffrey, Enrique A. Dalmasso, Siyu Fu, Thang Pham, Jianfeng Mei, Jaclyn J. Ho, Wenyong Zhang, Peter Lopez, David D. Ho. Contribution of Human {alpha}-Defensin-1, -2 and -3 to the Anti-HIV-1 Activity of CD8 Antiviral Factor. Science. 2002; 298:995-1000. [view]
• Markowitz M, Louie M, Hurley A, Sun E, Di Mascio M, Perelson AS, Ho DD. A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo. J Virol. 2003 Apr;77(8):5037-8. [view]
• Ho DD. A Shot in the Arm for AIDS Vaccine Research. PLoS Med. 2005 Jan 18;2(2):e36. [view]
• Chen Z, Zhang L, Qin C, Ba L, Yi CE, Zhang F, Wei Q, He T, Yu W, Yu J, Gao H, Tu X, Gettie A, Farzan M, Yuen KY, Ho DD. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J Virol. 2005 Mar;79(5):2678-88. [view]
• Markowitz M, Mohri H, Mehandru S, Shet A, Berry L, Kalyanaraman R, Kim A, Chung C, Jean-Pierre P, Horowitz A, La Mar M, Wrin T, Parkin N, Poles M, Petropoulos C, Mullen M, Boden D, Ho DD. Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report. Lancet. 2005 Mar 16;365(9464):1031-8. [view]
• Huang Y, Chen Z, Zhang W, Gurner D, Song Y, Gardiner DF, Ho DD. Design, Construction, and Characterization of a Dual-Promoter Multigenic DNA Vaccine Directed Against an HIV-1 Subtype C/B' Recombinant. J Acquir Immune Defic Syndr. 2008 Apr 1;47(4):403-11. [view]
• Chen Z, Huang Y, Zhao X, Ba L, Zhang W, Ho DD. Design, construction, and characterization of a multigenic modified vaccinia ankara candidate vaccine against human immunodeficiency virus type 1 subtype c/b'. J Acquir Immune Defic Syndr. 2008 Apr 1;47(4):412-21. [view]
• Lu L, Jia M, Ma Y, Yang L, Chen Z, Ho DD, Jiang Y, Zhang L. Changing faces of HIV infection in Yunnan, China. Nature 2008; 455:609-611. [view]
• Chen MW, Cheng T-J R, Huang Y, Jan J-T, Ma S-H, Yu AL, Wong C-H, Ho DD. A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses. Proc. Natl. Acad. Sci. USA 2008; 105:13538-13543. [view]
• Ho DD, Bieniasz PD. HIV-1 at 25. Cell 2008; 133:561-565. [view]
• Chen HY, Di Mascio M, Perelson AS, Ho DD, Zhang L. Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques. Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19079-84. [view]
• Gardiner DF, Rosenberg T, Zaharatos J, Franco D, Ho DD. A DNA vaccine targeting the receptor-binding domain of Clostridium difficile toxin A. Vaccine. 2009 Jun 2;27(27):3598-604. [view]
• Liang K, Gui X, Zhang YZ, Zhuang K, Meyers K, Ho DD. A case series of 104 women infected with HIV-1 via blood transfusion postnatally: high rate of HIV-1 transmission to infants through breast-feeding. J Infect Dis. 2009 Sep 1;200(5):682-6. [view]
• Scheid JF, Mouquet H, Feldhahn N, Seaman MS, Velinzon K, Pietzsch J, Ott RG, Anthony RM, Zebroski H, Hurley A, Phogat A, Chakrabarti B, Li Y, Connors M, Pereyra F, Walker BD, Wardemann H, Ho D, Wyatt RT, Mascola JR, Ravetch JV, Nussenzweig MC. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature. 2009 Apr 2;458(7238):636-40. [view]
• Zhou A, Meyers K, Li X, Chen Q, Qian HY, Lao Y, Geng E, Fan Y, Yang S, Chiu M, Ho DD. Prevention of mother-to-child transmission of HIV-1 using highly active anti-retroviral therapy in rural Yunnan, China. JAIDS 2010; 53(1): S15-22. [view]
• Sandhya Vasan, Sarah J. Schlesinger, Yaoxing Huang, Arlene Hurley, Angela Lombardo, Zhiwei Chen1, Soe Than, Phumla Adesanya, Catherine Bunce, Mark Boaz, Rosanne Boyle, Eddy Sayeed, Lorna Clark, Daniel Dugin1, Claudia Schmidt, Yang Song, Laura Seamons, Len Dally, Martin Ho, Carol Smith, Martin Markowitz, Josephine Cox, Dilbinder K. Gill, Jill Gilmour, Michael C. Keefer, Patricia Fast,Ho DD. Phase 1 Safety and Immunogenicity Evaluation of ADVAX, a Multigenic, DNA-Based Clade C/B’ HIV-1 Candidate Vaccine. Plos One 2010; 5:1-7. [view]
• Sandhya Vasan, Sarah J. Schlesinger, Zhiwei Chen, Arlene Hurley, Angela Lombardo, Soe Than, Phumla Adesanya, Catherine Bunce, Mark Boaz, Rosanne Boyle, Eddy Sayeed, Lorna Clark, Daniel Dugin, Mar Boente-Carrera, Claudia Schmidt, Qing Fang, LeiBa1, Yaoxing Huang, Gerasimos J. Zaharatos1, David F. Gardiner, Marina Caskey, Laura Seamons, Martin Ho, Len Dally, Carol Smith, Josephine Cox, Dilbinder Gill, Jill Gilmour, Michael C. Keefer, Patricia Fast, David D. Ho Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-HIV-1 B’/C Candidate Vaccine. Plos One 2010; 5:1-7. [view]
• Li X, Fujio M, Imamura M, Wu D, Vasan S, Wong CH, Ho DD, Tsuji M. Design of a potent CD1d-binding NKT cell ligand as a vaccine adjuvant. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13010-5. [view]
• Song R, Franco D, Kao CY, Yu F, Huang Y, Ho DD. Epitope mapping of ibalizumab, a humanized anti-CD4 monoclonal antibody with anti-HIV-1 activity in infected patients. J Virol. 2010 Jul;84(14):6935-42. [view]
• Franco D, Li W, Qing F, Stoyanov CT, Moran T, Rice CM, Ho DD. Evaluation of yellow fever virus 17D strain as a new vector for HIV-1 vaccine development. Vaccine. 2010 Aug 9;28(35):5676-85. [view]
• Mouquet H, Scheid JF, Zoller MJ, Krogsgaard M, Ott RG, Shukair S, Artyomov MN, Pietzsch J, Connors M, Pereyra F, Walker BD, Ho DD, Wilson PC, Seaman MS, Eisen HN, Chakraborty AK, Hope TJ, Ravetch JV, Wardemann H, Nussenzweig MC. Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation. Nature. 2010 Sep 30;467(7315):591-5. [view]
• Freeman MM, Seaman MS, Rits-Volloch S, Hong X, Kao CY, Ho DD, Chen B. Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody. Structure. 2010 Dec 8;18(12):1632-41. [view]
• Vasan S, Hurley A, Schlesinger SJ, Hannaman D, Gardiner DF, Dugin DP, Boente-Carrera M, Vittorino R, Caskey M, Andersen J, Huang YX, Cox JH, Tarragona-Fiol T, Gill DK, Cheeseman H, Clark L, Dally L, Smith C, Schmidt C, Park HH, Kopycinski JT, Gilmour J, Fast P, Bernard R, Ho DD. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS One. 2011;6(5):e19252. [view]
• Zaharatos GJ, Yu J, Pace C, Song Y, Vasan S, Ho DD, Huang YX. HIV-1 and influenza antigens synthetically linked to IgG2a Fc elicit superior humoral responses compared to unmodified antigens in mice. Vaccine. 2011 Dec 9;30(1):42-50. [view]
• Pace CS, Song R, Franco D, Seaman M, Ho DD. Bispecific Fusion Antibodies PG9-Ibalizumab (PG9-iMab) and VRC01-Ibalizumab (VRC01-iMab) Exhibit 100% Breadth and Picomolar Potency. AIDS RES HUM RETROVIRUS 2011 OCT;27(10):A15
• Chen MW, Liao HY, Huang YX, Jan JT, Huang CC, Ren CT, Wu CY, Cheng TJR, Ho DD, Wong CH. Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3510-5. [view]
• Pace CS, Fordyce MW, Franco D, Kao CY, Seaman MS, Ho DD. Anti-CD4 monoclonal antibody ibalizumab exhibits breadth and potency against HIV-1, with natural resistance mediated by the loss of a V5 glycan in envelope. 2013 Jan 1;62(1):1-9. [view]

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David Ho	Scientific Director and CEO, ADARC Irene Diamond Professor, Physician, Rockefeller University
Chasity Andrews	Post Doctoral Fellow
Maria Mar Boente-Carrera	Vaccine Clinical Laboratory Coordinator
Ming Wei Chen	Post Doctoral Fellow
Agegnehu Gettie	Sr. Scientific Program Administrator
Chandrabali Ghose-Paul	Research Scientist
Timothy Klemt	Administrative Assistant
Yang Luo	Post Doctoral Fellow
Kathrine Meyers	Program Manager, China AIDS Initiative
Kevin Mohammed	Post Doc
Mark Muesing	Senior Research Scientist
Craig Pace	Research Scientist
Neal Padte	Associate Director of Product Development
Fang Qing	Post Doctoral Fellow
Haoyu Qian	Project Coordinator, China AIDS Initiative
Ruijiang Song	Post Doctoral Fellow
Ming Sun	Visiting Scientist
Jian Yu	Post Doctoral Fellow

Dr. David Ho was named Man of the Year 1996 by Time Magazine. Dr. David Ho discusses the evolution of HIV/AIDS treatment, and the challenges in developing a vaccine on PBS’s The Charlie Rose Show. Dr. David Ho's talk on Mother-to-Child Transmission of HIV: A Tale of Two Provinces in China at ADARC noon seminar. Dr. David Ho: The Man Who Could Beat AIDS featured by Time Magazine 2010. Dr. Ho was named the most influential people of the last decade by China Newsweek 2010 (in Chinese). Dr. Ho discusses The HIV/AIDS Drug 'Cocktail' on Big Tank - Moments of Genius. Dr. David Ho Lectures at Quinnipiac University.