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Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors
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Journal Article
Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors
2013
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ Antibodies, Neutralizing - immunology
/ Antigens
/ Design
/ Epitopes
/ HIV
/ HIV 1
/ HIV Envelope Protein gp120 - chemistry
/ HIV Envelope Protein gp120 - genetics
/ HIV Envelope Protein gp120 - immunology
/ HIV Infections - prevention & control
/ Human immunodeficiency virus
/ Human immunodeficiency virus 1
/ Humans
/ Macaca
/ Mice
/ patients
/ Proteins
/ Receptors, Antigen, B-Cell - immunology
/ Vaccines
