Neutralization resistant HIV-1 primary isolates from antiretroviral naïve chronically infected children in India

- First time generated HIV-1 subtype C primary isolates from infected Indian children.
- evaluated neutralization susceptibility of primary isolates to new generation bNAbs.
- Majority of pediatric primary isolates were resistant to neutralization by Nabs.
- AIIMS_329 isolate was efficiently neutralized by PG9 and PG16 bNAbs.
- Pediatric isolates should be used to screen NAbs as vaccine candidates in children.

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 IC50 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.