Barnes, Christopher O., Schoofs, Till, Gnanapragasam, Priyanthi N. P., Golijanin, Jovana, Huey-Tubman, Kathryn E., Gruell, Henning, Schommers, Philipp ORCID: 0000-0003-3375-6800, Suh-Toma, Nina, Lee, Yu Erica, Lorenzi, Julio C. Cetrulo, Piechocka-Trocha, Alicja, Scheid, Johannes F., Jr, Anthony P. West, Walker, Bruce D., Seaman, Michael S., Klein, Florian ORCID: 0000-0003-1376-1792, Nussenzweig, Michel C. and Bjorkman, Pamela J. (2022). A naturally arising broad and potent CD4-binding site antibody with low somatic mutation. Sci. Adv., 8 (32). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 2375-2548

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Abstract

The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-angstrom x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Barnes, Christopher O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoofs, TillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gnanapragasam, Priyanthi N. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Golijanin, JovanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huey-Tubman, Kathryn E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruell, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schommers, PhilippUNSPECIFIEDorcid.org/0000-0003-3375-6800UNSPECIFIED
Suh-Toma, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Yu EricaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lorenzi, Julio C. CetruloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piechocka-Trocha, AlicjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheid, Johannes F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jr, Anthony P. WestUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walker, Bruce D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seaman, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDorcid.org/0000-0003-1376-1792UNSPECIFIED
Nussenzweig, Michel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjorkman, Pamela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-693335
DOI: 10.1126/sciadv.abp8155
Journal or Publication Title: Sci. Adv.
Volume: 8
Number: 32
Date: 2022
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 2375-2548
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NEUTRALIZING ANTIBODIES; GENETIC-DETERMINANTS; HIV-ANTIBODY; B-CELLS; CD4; IDENTIFICATION; VACCINE; REPERTOIRE; SEQUENCE; REVEALSMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69333

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