Schommers, Philipp ORCID: 0000-0003-3375-6800, Gruell, Henning, Abernathy, Morgan E., Tran, My-Kim, Dingens, Adam S., Gristick, Harry B., Barnes, Christopher O., Schoofs, Till, Schlotz, Maike, Vanshylla, Kanika, Kreer, Christoph, Weiland, Daniela, Holtick, Udo, Scheid, Christof, Valter, Markus M., van Gils, Marit J. ORCID: 0000-0003-3422-8161, Sanders, Rogier W., Vehreschild, Joerg J., Cornely, Oliver A., Lehmann, Clara, Faetkenheuer, Gerd, Seaman, Michael S., Bloom, Jesse D., Bjorkman, Pamela J. and Klein, Florian (2020). Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell, 180 (3). S. 471 - 512. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V(H)1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC50 = 0.048 mu g/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-angstrom cryo-EM structure of a 1-18-BG505(SOSIP.664) Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schommers, PhilippUNSPECIFIEDorcid.org/0000-0003-3375-6800UNSPECIFIED
Gruell, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abernathy, Morgan E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tran, My-KimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dingens, Adam S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gristick, Harry B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barnes, Christopher O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoofs, TillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlotz, MaikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vanshylla, KanikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreer, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiland, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holtick, UdoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheid, ChristofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valter, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Gils, Marit J.UNSPECIFIEDorcid.org/0000-0003-3422-8161UNSPECIFIED
Sanders, Rogier W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vehreschild, Joerg J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cornely, Oliver A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faetkenheuer, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seaman, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloom, Jesse D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjorkman, Pamela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-345362
DOI: 10.1016/j.cell.2020.01.010
Journal or Publication Title: Cell
Volume: 180
Number: 3
Page Range: S. 471 - 512
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CRYO-EM STRUCTURE; MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; MATURATION PATHWAY; DISULFIDE BONDS; DURABLE CONTROL; FITNESS COST; SINGLE-CELL; CD4; PROTECTIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34536

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