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TitleImmunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.
Journal, issue, pagesNature, Year 2019
Publish dateMay 29, 2019
AuthorsAmelia Escolano / Harry B Gristick / Morgan E Abernathy / Julia Merkenschlager / Rajeev Gautam / Thiago Y Oliveira / Joy Pai / Anthony P West / Christopher O Barnes / Alexander A Cohen / Haoqing Wang / Jovana Golijanin / Daniel Yost / Jennifer R Keeffe / Zijun Wang / Peng Zhao / Kai-Hui Yao / Jens Bauer / Lilian Nogueira / Han Gao / Alisa V Voll / David C Montefiori / Michael S Seaman / Anna Gazumyan / Murillo Silva / Andrew T McGuire / Leonidas Stamatatos / Darrell J Irvine / Lance Wells / Malcolm A Martin / Pamela J Bjorkman / Michel C Nussenzweig /
PubMed AbstractBroadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it ...Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.
External linksPubMed:31142836 / Publisher's page
KeywordsVIRAL PROTEIN/Immune System / HIV-1 broadly-neutralizing antibody / Env trimer structure / V3-glycan patch / cryo-EM / RC1 / immunogen design / ANTIVIRAL PROTEIN-IMMUNE SYSTEM complex / ANTIVIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / VIRAL PROTEIN-IMMUNE SYSTEM complex
MethodsEM (single particle)
Resolution3.9 - 4.4 A
Structure data

EMDB-20175:
Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch bNAb 10-1074

EMDB-20176:
Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab874NHP

EMDB-20177:
Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab897NHP

EMDB-20178:
Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab275MUR

PDB-6orn:
Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch bNAb 10-1074

PDB-6oro:
Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab874NHP

PDB-6orp:
Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab897NHP

PDB-6orq:
Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab275MUR

Chemicals

ChemComp-NAG:
N-ACETYL-D-GLUCOSAMINEN-Acetylglucosamine

ChemComp-BMA:
BETA-D-MANNOSEMannose

ChemComp-MAN:
ALPHA-D-MANNOSEMannose

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
  • macaca mulatta (Rhesus monkey)
  • Mus musculoides (Temminck's mouse)
  • mus musculus (house mouse)

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