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.
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.