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Challenges for structure-based HIV vaccine design

Schief, William Ra; Ban, Yih-En Andrewa; Stamatatos, Leonidasb,c

Current Opinion in HIV and AIDS: September 2009 - Volume 4 - Issue 5 - p 431–440
doi: 10.1097/COH.0b013e32832e6184
Neutralizing antibodies: Edited by David Montefiori and John Mascola
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Purpose of review We review structural information on the native HIV envelope trimer and the known epitopes for broadly neutralizing antibodies and discuss how this structural information should guide the design of more effective immunogens.

Recent findings Recent epitope mapping of HIV-positive sera demonstrates that the immune system is able to mount a potent and broadly neutralizing antibody response against conserved elements of the HIV envelope. The structure of trimeric envelope spikes on intact HIV-1 virions (the target of neutralizing antibodies) was determined at low resolution using cryo-electron tomography. Fitting high-resolution crystal structures of monomeric gp120 complexed with different neutralizing ligands into the cryo-electron density maps provides useful models for the native virion trimer and for mechanisms of neutralization.

Summary So far, all attempts to elicit broadly neutralizing antibodies against HIV by immunization have failed. Recent structural information on the virion-associated HIV envelope spike and of the precise interaction of broadly neutralizing mAbs with their epitopes clarifies the steric and geometric constraints faced by antibodies targeting conserved HIV epitopes. Implications for vaccine design are discussed.

aDepartment of Biochemistry, University of Washington, USA

bSeattle Biomedical Research Institute, USA

cDepartment of Global Health, University of Washington, Seattle, Washington, USA

Correspondence to William R. Schief, Department of Biochemistry, University of Washington, Seattle, WA 98195, USA Tel: +1 206 616 7542; fax: +1 206 685 1792; e-mail: schief@u.washington.edu

© 2009 Lippincott Williams & Wilkins, Inc.