Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.
Cell
; 166(6): 1471-1484.e18, 2016 Sep 08.
Article
em En
| MEDLINE
| ID: mdl-27610571
ABSTRACT
The design of immunogens that elicit broadly reactive neutralizing antibodies (bnAbs) has been a major obstacle to HIV-1 vaccine development. One approach to assess potential immunogens is to use mice expressing precursors of human bnAbs as vaccination models. The bnAbs of the VRC01-class derive from the IGHV1-2 immunoglobulin heavy chain and neutralize a wide spectrum of HIV-1 strains via targeting the CD4 binding site of the envelope glycoprotein gp120. We now describe a mouse vaccination model that allows a germline human IGHV1-2(∗)02 segment to undergo normal V(D)J recombination and, thereby, leads to the generation of peripheral B cells that express a highly diverse repertoire of VRC01-related receptors. When sequentially immunized with modified gp120 glycoproteins designed to engage VRC01 germline and intermediate antibodies, IGHV1-2(∗)02-rearranging mice, which also express a VRC01-antibody precursor light chain, can support the affinity maturation of VRC01 precursor antibodies into HIV-neutralizing antibody lineages.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
HIV-1
/
Imunização
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Cadeias Pesadas de Imunoglobulinas
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Células Precursoras de Linfócitos B
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Anticorpos Neutralizantes
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Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article