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bioRxiv · 10.1101/2023.01.19.524673

Recognition determinants of broad and potent HIV-1 neutralization by an affinity matured antibody from a pediatric elite-neutralizer

Kumar, S.·Singh, S.·Chatterjee, A.·Bajpai, P.·Sharma, S.·Katpara, S.·Lodha, R.·Dutta, S.·Luthra, K.
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Abstract

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 {micro}g/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[A] 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.

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Kumar, S., Singh, S., Chatterjee, A., Bajpai, P., Sharma, S., Katpara, S., Lodha, R., Dutta, S., Luthra, K.. 2023-01-20. Recognition determinants of broad and potent HIV-1 neutralization by an affinity matured antibody from a pediatric elite-neutralizer. https://doi.org/10.1101/2023.01.19.524673

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