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-Structure paper
タイトル | Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody. |
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ジャーナル・号・ページ | iScience, Vol. 26, Issue 9, Page 107579, Year 2023 |
掲載日 | 2023年9月15日 |
著者 | Sanjeev Kumar / Swarandeep Singh / Arnab Chatterjee / Prashant Bajpai / Shaifali Sharma / Sanket Katpara / Rakesh Lodha / Somnath Dutta / Kalpana Luthra / |
PubMed 要旨 | 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 ...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 IC 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 Å 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. |
リンク | iScience / PubMed:37649696 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.4 Å |
構造データ | EMDB-36815: Recognition determinants of broad and potent HIV-1 neutralization by an affinity matured antibody from a pediatric elite-neutralizer |
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