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Broad and potent neutralizing antibodies (bnAbs) with multiple epitope specificities evolve in HIV-1 infected children. Herein, we studied two antiretroviral naïve chronically HIV-1C in fected monozygotic pediatric twins AIIMS_329 and AIIMS_330 with potent plasma bnAbs. Elite plasma neutralizing activity was observed since initial sampling at 78 months in AIIMS_330 and persisted throughout, while in AIIMS_329 it was seen at 90-months of age after which potency decreased overtime. We evaluated potential viral characteristics associat ed with varied immune profile by generating single genome amplified pseudoviruses. The AIIMS_329 viruses generated from 90-month time point were neutralization sensitive to bnAbs and contemporaneous plasma antibodies, while viruses from 112-month and 117-month timepoints were resistant to most bnAbs and contemporaneous plasma. AIIMS_329 viruses developed resistance to plasma nAbs plausibly by N160-glycan loss, V1- and V4- loop lengthening. The viruses generated from AIIMS_330 (at 90 and 117-months) showed varied susceptibility to bnAbs and autologous contemporaneous plasma antibodies while the viruses of 112-month timepoint, at which plasma nAb specificities mapped to the V2-glycan, V3-glycan and CD4bs, were resistant to contemporaneous plasma antibodies as well as to most bnAbs. Chimeric viruses were constructed from 90-month time-point PG9 sensitive AIIMS-329 and AIIMS_330 viruses with swapped V1V2 regions of their respective evolved viruses (at 112 and 117-month), that led to higher resistance to neutralization by PG9 and autologous plasma antibodies. We observed evolution of a viral pool in AIIMS_330 donor, comprising of plasma antibody neutralization sensitive or resistant diverse autologous viruses that may have contributed to development and maintenance of elite neutralizing activity. [ABSTRACT FROM AUTHOR]

Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been extensively tested against pesudoviruses of diverse strains. We generated and characterized HIV-1 primary isolates from antiretroviral naïve infected Indian children, and determined their susceptibility to known NAbs. All the 8 isolates belonged to subtype-C and were R5 tropic. Majority of these viruses were resistant to neutralization by NAbs, suggesting that the bnAbs, known to efficiently neutralize pseudoviruses (adult and pediatric) of different strains, are less effective against pediatric primary isolates. Interestingly, AIIMS_329 isolate displayed high susceptibility to neutralization by PG9 and PG16bnAbs, with IC 50 titer of 1.3 and 0.97 μg/ml, suggesting exposure of this epitope on this virus. All isolates except AIIMS_506 were neutralized by contemporaneous plasma antibodies. Our findings suggest that primary isolates, due to close resemblance to viruses in natural infection, should be used to evaluate NAbs as effective vaccine candidates in both children and adults. [ABSTRACT FROM AUTHOR]