Challenges for structure-based HIV vaccine design.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Schief
William R
WR
Department of Biochemistry, University of Washington, Seattle, USA. schief@u.washington.edu
Ban
Yih-En Andrew
YE
Stamatatos
Leonidas
L
D016915:AIDS Vaccines / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000276:immunology*
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus