Director Viral Immunology, IAVI's Neutralizing Antibody Center
Faculty, Graduate Program
HIV-1 Envelope Glycoprotein Structure and Immunogenicity
The human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS causing a huge toll of human malaise and morbidity. Although a substantial arsenal of drugs can treat this devastating disease, a broadly effective vaccine remains the most cost-effective way to halt further spread of this virus in the human population. However, due to the approximately 32 million infected individuals already infected in the human population world-wide, and the incredible diversity of this virus in the individual and the population, such a vaccine has proven difficult to develop. Because most viral vaccines protect against disease by neutralizing antibodies, we study the HIV-1 envelope glycoproteins (Env) as antigens, as immunogens and at the atomic level of structural refinement to gain insight in how to better elicit antibodies directed against these external, variable and heavily glycosylated neutralizing determinants. We make specialized Env variants and analyze their biochemical and biophysical features, use them as probes to isolate new and novel broadly neutralizing antibodies and assess their immunogenicity all as part of the plan to better elicit neutralizing antibodies by rational, structure-guided vaccine design.
Ph.D. (Immunology), Tufts University, School of Medicine 1991
M.S. (Biology), Southern Connecticut State University 1982
B.S. (Biology), Trinity College 1974
2007-2009 Senior Investigator (tenure), Chief, Structural Virology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
2001-2006 Investigator, Chief, Structural Virology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
1999-2000 Instructor, Department of Medicine, Harvard Medical School, Harvard University
1997-2000 Instructor, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute
1994-1999 Instructor, Department of Pathology, Harvard Medical School, Harvard University
1994-1997 Instructor, Division of Human Retrovirology, Dana-Farber Cancer Institute
1991-1994 Research Fellow, Department of Pathology, Dana-Farber Cancer Institute
1991-1994 Research Fellow, Division of Human Retrovirology, Dana-Farber Cancer Institute
1991-1993 Research Fellow, NIAID AIDS Postdoctoral Training Grant, Dana-Farber Cancer Institute
1998-present: Member of the American Foundation for AIDS Research (AmFAR) Scientific Advisory Committee 1998 - Presenter to the Dana-Farber Cancer Institute Scientific Advisory Board 2006 - 2009 Member – NIAID Promotion and Tenure Title 42 Sub Committee 1996 - present: Member of the American Association for the Advancement of Science 2000 - present: Member of the American Microbiology Association 2000 -present: Charter member of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Consortium (NAC)
2005 - present: Journal of Virology 2002 - present: Aids Fonds Grant Applications, Netherlands
Li Y, Migueles SA, Welcher B, Svehla K, Phogat A, Louder MK, Wu X, Shaw GM, Connors M, Wyatt RT, Mascola JR. Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat Med. 2007 Sep;13(9):1032-4.
Karlsson Hedestam GB, Fouchier RA, Phogat S, Burton DR, Sodroski J, Wyatt RT. The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus. Nat Rev Microbiol. 2008 Feb;6(2):143-55.
Dey B, Svehla K, Xu L, Wycuff D, Zhou T, Voss G, Phogat A, Chakrabarti BK, Li Y, Shaw G, Kwong PD, Nabel GJ, Mascola JR, Wyatt RT. Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site. PLoS Pathog. 2009 May;5(5):e1000445.
Li Y, Svehla K, Louder MK, Wycuff D, Phogat S, Tang M, Migueles SA, Wu X, Phogat A, Shaw GM, Connors M, Hoxie J, Mascola JR, Wyatt R. Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals. J Virol. 2009 Jan;83(2):1045-59.