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We have previously shown that HIV-1 infected children develop broader and more potent neutralizing antibody responses than adults. This study aimed to determine the antibody specificities in 16 HIV-1 subtype C infected children who displayed exceptional neutralization breadth on a 22 multi-subtype virus panel. All children were ART-naive with normal CD4 counts despite being infected for a median of 10.1 years with high viral loads. The specificity of bNAbs was determined using epitope37 ablating mutants, chimeric constructs and depletion or inhibition of activity with peptides and glycoproteins. We found that bNAbs in children largely targeted previously defined epitopes, including the V2-glycan, V3-glycan, CD4bs and gp120- gp41 interface. Remarkably, 63% of children had antibodies targeting 2 or 3 and in one case 4 of these bNAb epitopes. Longitudinal analysis of plasma from a mother42 child pair over 9 years showed that while they both had similar neutralization profiles, the antibody specificities differed. The mother developed antibodies targeting the V2- glycan and CD4bs whereas bNAb specificities in the child could not be mapped until 6 years when a minor V2-glycan response appeared. The child also developed high titre MPER binding antibodies, not seen in the mother, although these were not a major bNAb specificity. Overall, exceptional neutralization breadth in this group of children may be the result of extended exposure to high antigenic load in the context of an intact immune system, which allowed for the activation of multiple B cell lineages and the generation of polyclonal responses targeting several bNAb epitopes. IMPORTANCE An HIV vaccine is likely to require broadly neutralizing antibodies (bNAbs), which have been shown to prevent HIV acquisition in non-human primates. Recent evidence suggests that HIV-infected children may be inherently better at generating bNAbs than adults. Here, we show that exceptional neutralization breadth in a group of viremic HIV-1 subtype C infected children was due to the presence of polyclonal bNAb antibody responses. These bNAbs targeted multiple epitopes on the HIV envelope glycoprotein previously defined in adult infection, suggesting that the immature immune system recognizes HIV antigens similarly. Since elicitation of a polyclonal bNAb response is the basis of next generation HIV envelope vaccines, further studies of how bNAb lineages are stimulated in children is warranted. Furthermore, our findings suggest that children may respond particularly well to vaccines designed to elicit antibodies to multiple bNAb epitopes. [ABSTRACT FROM AUTHOR]