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Science. 2013 May 10;340(6133):711-6. doi: 10.1126/science.1234150. Epub 2013 Mar 28.

Rational HIV immunogen design to target specific germline B cell receptors.

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  • 1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors, and elucidated germline binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens.

PMID:
23539181
[PubMed - indexed for MEDLINE]
PMCID:
PMC3689846
Free PMC Article

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