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TitleA broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateOct 21, 2020
AuthorsZijun Wang / Christopher O Barnes / Rajeev Gautam / Julio C Cetrulo Lorenzi / Christian T Mayer / Thiago Y Oliveira / Victor Ramos / Melissa Cipolla / Kristie M Gordon / Harry B Gristick / Anthony P West / Yoshiaki Nishimura / Henna Raina / Michael S Seaman / Anna Gazumyan / Malcolm Martin / Pamela J Bjorkman / Michel C Nussenzweig / Amelia Escolano /
PubMed AbstractA small fraction of HIV-1- infected humans develop broadly neutralizing antibodies (bNAbs) against HIV-1 that protect macaques from simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a ...A small fraction of HIV-1- infected humans develop broadly neutralizing antibodies (bNAbs) against HIV-1 that protect macaques from simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs develop broadly neutralizing serologic activity, but less is known about the nature of simian antibodies. Here, we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8 that developed broadly neutralizing serologic activity targeting the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1% of HIV-1 isolates in a 42-pseudovirus panel with a geometric mean IC50 of 0.055 µg/mLl and SHIVAD8 with an IC50 of 0.028 µg/mLl. Ab1485 binds the V3-glycan epitope in a glycan-dependent manner. A 3.5 Å cryo-electron microscopy structure of Ab1485 in complex with a native-like SOSIP Env trimer showed conserved contacts with the N332gp120 glycan and gp120 GDIR peptide motif, but in a distinct Env-binding orientation relative to human V3/N332gp120 glycan-targeting bNAbs. Intravenous infusion of Ab1485 protected macaques from a high dose challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs.
External linksElife / PubMed:33084569 / PubMed Central
MethodsEM (single particle)
Resolution3.55 Å
Structure data

22820

7kde

EMDB-22820, PDB-7kde:
BG505 SOSIP.664 in complex with the V3-targeting rhesus macaque antibody 1485 and human gp120-gp41 interface antibody 8ANC195
Method: EM (single particle) / Resolution: 3.55 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN/Immune System / HIV-1 / broadly neutralizing antibody / Env / envelope / BG505 / bNAb / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex

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