Broadly neutralizing antibodies (
bnAbs) have been considered to be potent therapeutic tools and potential
vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of
bnAbs has been associated with enhanced exposure to
antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of
bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global
HIV infections, the identification of
bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV
therapy and prevention. In the present study, we analysed and compared the neutralization potential of responses in 70 plasma samples isolated from ART-naïve HIV-1 subtype C-infected individuals with various
disease progression profiles against a panel of 30 pseudoviruses. Among the seven samples that exhibited a neutralization breadth of ≥70 %, four were identified as 'elite neutralizers', and three of these were from viraemic non-progressors while the fourth was from a typical progressor. Analysis of the neutralization specificities revealed that none of the four elite neutralizers were reactive to
epitopes in the membrane proximal external region (MPER), CD4-binding site and V1V2 or V3
glycan. However, two of the four elite neutralizers exhibited enhanced sensitivity towards viruses lacking N332
glycan, indicating high neutralization potency. Overall, our findings indicate that the identification of potent neutralization responses with distinct
epitope specificities is possible from the as yet unexplored Indian population, which has a high prevalence of HIV-1 subtype C
infection.