Universität zu Köln

Dam, Kim-Marie A., Barnes, Christopher O., Gristick, Harry B., Schoofs, Till, Gnanapragasam, Priyanthi N. P., Nussenzweig, Michel C. and Bjorkman, Pamela J. (2022). HIV-1 CD4-binding site germline antibody-Env structures inform vaccine design. Nat. Commun., 13 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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Abstract

BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs. To understand how SHMs correlate with BG24 neutralization of HIV-1, we report 4.1 angstrom and 3.4 angstrom single-particle cryo-EM structures of two inferred germline (iGL) BG24 precursors complexed with engineered Env-based immunogens lacking CD4bs N-glycans. Structures reveal critical Env contacts by BG24(iGL) and identify antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24(iGL) variants bound to Envs with CD4bs glycans present provide insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276(gp120) glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dam, Kim-Marie A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barnes, Christopher O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gristick, Harry B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoofs, Till UNSPECIFIED UNSPECIFIED UNSPECIFIED Gnanapragasam, Priyanthi N. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nussenzweig, Michel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bjorkman, Pamela J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-688770
DOI:	10.1038/s41467-022-33860-2
Journal or Publication Title:	Nat. Commun.
Volume:	13
Number:	1
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CRYO-EM; NEUTRALIZING ANTIBODIES; VRC01; RECOGNITION; MATURATION; BROAD; CD4; VISUALIZATION; TRIMERS; REVEALS Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68877