Selection of HIV Envelope Strains for Standardized Assessments of Vaccine-Elicited Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies
Dieter Mielke, Sherry Stanfield-Oakley, Bhavesh Borate, Leigh H. Fisher, Katelyn Faircloth, Marina Tuyishime, Kelli Greene, Hongmei Gao, Carolyn Williamson, Lynn Morris, Christina Ochsenbauer, Georgia D. Tomaras, Barton F. Haynes, David C. Montefiori, Justin Pollara, Allan C. deCamp, Guido Ferrari
Abstract
Antibody-dependent cellular cytotoxicity (ADCC) responses were found to correlate with reduced risk of infection in the RV144 trial of the only human HIV-1 vaccine to show any efficacy to date. However, reagents to understand the breadth and magnitude of these responses across preclinical and clinical vaccine trials remain underdeveloped. In this study, we characterize HIV-1 infectious molecular clones encoding 29 distinct Envelope strains (Env-IMCs) to understand factors that impact virus susceptibility to ADCC and use statistical methods to identify smaller nested panels of four to eight Env-IMCs that accurately represent the full set. These reagents can be used as standardized reagents across studies to fully understand how ADCC may affect efficacy of future vaccine studies and how studies differ in the breadth of responses developed.