Natural Killer cells: B35/53Bw4TTC2 & bnAbs

Studies in early-ART-treated infants and adults and in SIV-infected non-human primates suggest that particular NK responses may significantly reduce the viral reservoir, improving cure potential. A specific immunogenetic signature, ‘B35/53Bw4TTC2’, identified in the adult VISCONTI cohort of post-treatment controllers is hypothesised to carry a 50% likelihood of cure. We also hypothesise that in a South African population, where CMV infection is endemic in infancy, a memory-like NK response may contribute to a more effective NK response against HIV. Our work, led by Vinicius Vieira, looks to define whether this B35/53Bw4TTC2 signature, and the associated NK responses, are present in early-ART-treated children and mothers from the Babycure cohort and whether they are associated with low viral reservoirs and high cure potential.

In our studies of HIV-uninfected children we see expansion of both CD56^hi and CD16^hi NK subsets in children aged 5-14yrs compared to younger children and adults. The CD56^hi subset is especially depleted and dysfunctional in ART-naïve HIV-infected children (Singh et al., 2020). In view of the potential for NK cells to reduce the size of the HIV reservoir via bnAb-mediated ADCC we are studying the ontogeny of NK cell function to define the optimal timing for paediatric bnAb administration to maximise the chance of achieving cure in HIV-infected children.