Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Primary African Isolates

Novel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Broadly neutralizing human antibodies (bNAbs) with exceptional activity against HIV-1 are currently being tested in HIV-1 prevention trials. The selection of anti-HIV-1 bNAbs for clinical development was primarily guided by their in vitro neutralizing activity against HIV-1 Env-pseudotyped viruses. Here, we report on the neutralizing activity of 9 anti-HIV-1 bNAbs now in clinical development against 126 Glade A, C, and D peripheral blood mononuclear cell (PBMC)-derived primary African isolates. The neutralizing potency and breadth of the bNAbs tested were significantly reduced compared to those seen with pseudotyped-virus panels. The difference in sensitivity between pseudotyped viruses and primary isolates varied from 3- to nearly 100-fold depending on the bNAb and the HIV-1 Glade. Thus, the neutralizing activity of bNAbs against primary African isolates differs from their activity against pseudovirus panels. The data have significant implications for interpreting the results of ongoing HIV-1 prevention trials. IMPORTANCE HIV remains a major public health problem worldwide, and new therapies and preventive strategies are necessary for controlling the epidemic. Broadly neutralizing antibodies (bNAbs) have been developed in the past decade to fill this gap. The neutralizing activity of these antibodies against diverse HIV strains has mostly been measured using Env-pseudotyped viruses, which overestimate bNAb coverage and potency. In this study, we measured the neutralizing activity of nine bNAbs against Glade A, C, and D HIV isolates derived from cells of African patients living with HIV and produced in peripheral blood mononuclear cells. We found that the coverage and potency of bNAbs were often significantly lower than what was predicted by Env-pseudotyped viruses and that this decrease was related to the bNAb binding site class. These data are important for the planning and analysis of clinical trials that seek to evaluate bNAbs for the treatment and prevention of HIV infection in Africa.