B-106 Characterizing the basis for the broad and potent HIV-specific neutralizing antibody response of infants

Abstract

In the past few years, many new broad and potent HIV-specific monoclonal antibodies (Mabs) have been isolated from HIV-infected adults. However, because the breadth of these antibodies was acquired over many years, it will be challenging to elicit such Nabs with a vaccine. We found that HIV-infected infants often develop broad and potent HIV-specific Nab responses. Among 28 infants we identified 20 with cross clade Nab responses within the first two years of their infection, including a subset that neutralized Tier 2–3 variants from multiple clades. In some infants, there was evidence of cross clade breadth within the first year[LINE SEPARATOR]of their infection. To characterize these infant antibody responses, we isolated single B cells from sample from an infant with a cross clade Nab response at 336 days PI. We used a combination of sorting for B cells that bound envelope trimer as well as functional screening of cultured B cells for neutralizing activity to identify B cells of interest. Among those B cells identified through functional screening, there are 10 where we have rescued matched VH and VL chains. Six of these Mabs demonstrate some HIV-specific Tier 2 neutralizing activity and one Mab demonstrates potency similar to VRC01 for some viruses tested. In preliminary analysis using a small virus panel, these antibodies show distinct patterns of neutralization and no single Mab isolated to-date recapitulates the full breadth of the original plasma. None of the Mabs share a common VH or VL chain, suggesting that the broad antibody activity in this infant may be due to a polyclonal response.