Guiding the long way to broad HIV neutralization. Issue 3 (May 2017)

• Record Type: Journal Article
• Authors: Peterhoff, David; Wagner, Ralf
• Is Part Of: Current opinion in HIV & AIDS. Volume 12:Issue 3(2017:May)
• Publication Date: 2017-05
• Subjects: broadly neutralizing antibodies -- germline bnAb knock-in mouse models -- germline targeting immunogens -- guiding B-cell development -- HIV; AIDS (Disease) -- Periodicals; HIV infections -- Periodicals; HIV Infections -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; Infections à VIH -- Périodiques; Sida -- Périodiques; AIDS (Disease); HIV infections; Periodicals; 616.9792005
• DOI: 10.1097/COH.0000000000000356
• Languages: English
• ISSNs: 1746-630X

Abstract

Abstract : Purpose of review: It has been demonstrated that extensive virus diversification and antibody coevolution are necessary to give rise to broadly neutralizing antibodies targeting the envelope protein of HIV-1. Here, we discuss recent progress of vaccine design approaches aiming on strategies to initiate and guide B-cell development toward this outcome, as well as their evaluation in mouse models engineered to express human antibodies. Recent findings: Several specially tailored transgenic mouse strains have been developed to test the concept of engaging and guiding B-cell development by sequential immunizations. Currently available models display prerearranged or nonrearranged germline or mature VDJH and VJL loci of CD4-binding-site-specific (VRC01, 3BNC60) and high-mannose-patch-specific (PGT121) broadly neutralizing antibodies, or even the complete human V(D)J segments. Data generated in these knock-in mouse models elegantly prove the feasibility of the concept when using a carefully selected panel of engineered envelope proteins. Summary: Recent studies in knock-in transgenic mouse models provide a proof-of-concept that germline B-cell receptor targeting followed by sequential immunization can engage the respective naïve precursor B cells and guide B-cell receptor development toward broadly neutralizing reactivity.