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

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 (SHM) of 15.2%. 44m neutralized 79% of HIV-1 heterologous viruses tested, with a geometric mean IC50 titer of 0.36 ug/ml. The cryoEM structure of 44m Fab in complex with fully-cleaved glycosylated native-like BG505.SOSIP envelope trimer at 4.4 Angstrom 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 bnAb. This study 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. ### Competing Interest Statement The authors have declared no competing interest.