Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Primary African Isolates
Julio C. C. Lorenzi, Pilar Mendoza, Yehuda Z. Cohen, Lilian Nogueira, Christy L. Lavine, Joseph Sapiente, Marie Wiatr, Nelly Mugo, Andrew Mujugira, Sinéad Delany, Jairam R. Lingappa, Connie Celum, Michael S. Seaman, Marina Caskey, Michel C. Nussenzweig
Abstract
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 clade 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-psuedotyped viruses, and that this decrease was related to the bNAb biding site class. This data is important for the planning and analysis of clinical trials that seek to evaluate bNAbs for the treatment and prevention of HIV infection in Africa.