Cell-associated HIV infection may be a common mode of transmission and relatively hidden from neutralizing antibodies. Broadly neutralizing antibodies (BnAbs) protect macaques from cell-free SHIV challenge, but their efficacy against cell-associated SHIV is unclear. Antibody-dependent cellular cytotoxicity and NK cell responses may be important in antibody mediated clearance of cell-associated virus.
We infused pigtail macaques with the BnAb PGT121 or an isotype control and challenged animals one hour later intravenously with splenocytes from a SHIVSF162P3-infected donor.
All five controls had high-level viremia within one-week post challenge. Three of six PGT121-infused animals were completely protected from the cell-associated virus challenge, two of six had a short delay in onset of high-level viremia and one animal had a seven week delay in onset of viremia. The infused antibody had decayed on average to 2.0µg/ml by one-week post infusion and was well below 1µg/ml (range <0.1-0.8µg/ml) by eight weeks, coinciding viral recrudescence in one animal.
Our results show HIV-1-specific neutralizing antibodies have partial efficacy against a cell-associated virus exposure in macaques. We conclude that sustaining high concentrations of bioavailable BnAb is an important factor for protecting against cell-associated virus transmissions. Ongoing work is studying Fc-defective PGT121 and the importance of NK-cell mediated ADCC against lower dose challenges with cell-associated SHIV.