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Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody

Kumar, S and Singh, S and Chatterjee, A and Bajpai, P and Sharma, S and Katpara, S and Lodha, R and Dutta, S and Luthra, K (2023) Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody. In: iScience, 26 (9).

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Official URL: https://doi.org/10.1016/j.isci.2023.107579


The structural and characteristic features of HIV-1 broadly neutralizing antibodies (bnAbs) from chronically infected pediatric donors are currently unknown. Herein, we characterized a heavy chain matured HIV-1 bnAb 44m, identified from a pediatric elite-neutralizer. Interestingly, in comparison to its wild-type AIIMS-P01 bnAb, 44m exhibited moderately higher level of somatic hypermutations of 15.2. The 44m neutralized 79 of HIV-1 heterologous viruses (n = 58) tested, with a geometric mean IC50 titer of 0.36 μg/mL. The cryo-EM structure of 44m Fab in complex with fully cleaved glycosylated native-like BG505.SOSIP.664.T332N gp140 envelope trimer at 4.4 à resolution revealed that 44m targets the V3-glycan N332-supersite and GDIR motif to neutralize HIV-1 with improved potency and breadth, plausibly attributed by a matured heavy chain as compared to that of wild-type AIIMS-P01. This study further improves our understanding on pediatric HIV-1 bnAbs and structural basis of broad HIV-1 neutralization by 44m may be useful blueprint for vaccine design in future. © 2023 The Authors

Item Type: Journal Article
Publication: iScience
Publisher: Elsevier Inc.
Additional Information: The copyright for this article belongs to the Authors.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 08 Nov 2023 03:35
Last Modified: 08 Nov 2023 03:35
URI: https://eprints.iisc.ac.in/id/eprint/83031

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