Schoofs, Till, Barnes, Christopher O., Suh-Toma, Nina, Golijanin, Jovana, Schommers, Philipp ORCID: 0000-0003-3375-6800, Gruell, Henning, West, Anthony P., Jr., Bach, Franziska, Lee, Yu Erica, Nogueira, Lilian, Georgiev, Ivelin S., Bailer, Robert T., Czartoski, Julie, Mascola, John R., Seaman, Michael S., McElrath, M. Juliana, Doria-Rose, Nicole A., Klein, Florian, Nussenzweig, Michel C. and Bjorkman, Pamela J. (2019). Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope. Immunity, 50 (6). S. 1513 - 1539. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against Glade AE viruses, which o are poorly covered by V3-glycan bNAbs. A 3.3 angstrom cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silent-face antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448(gp)(120) glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schoofs, TillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barnes, Christopher O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suh-Toma, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Golijanin, JovanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schommers, PhilippUNSPECIFIEDorcid.org/0000-0003-3375-6800UNSPECIFIED
Gruell, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
West, Anthony P., Jr.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bach, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Yu EricaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nogueira, LilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Georgiev, Ivelin S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bailer, Robert T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czartoski, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mascola, John R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seaman, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McElrath, M. JulianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doria-Rose, Nicole A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nussenzweig, Michel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjorkman, Pamela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-137664
DOI: 10.1016/j.immuni.2019.04.014
Journal or Publication Title: Immunity
Volume: 50
Number: 6
Page Range: S. 1513 - 1539
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4180
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HUMAN MONOCLONAL-ANTIBODIES; STANDARDIZED ASSESSMENTS; VIRUS; VACCINE; PROTECTION; IDENTIFICATION; INFECTION; RESPONSES; SEQUENCE; BREADTHMultiple languages
ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13766

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