A Novel Methodology for Isolating Broadly Neutralizing HIV-1 Human Monoclonal Antibodies

Abstract

Background: Identification of broadly neutralizing HIV-1 human monoclonal antibodies (bnmAbs) may aid in development of an effective HIV-1/AIDS vaccine and antibody drugs for prevention and treatment of HIV-1 infection. Many HIV-1 bnmAbs have been identified from HIV-1-infected ‘‘elite controllers’’, especially in the past three years. Most of known bnmAbs were isolated based on their binding to HIV-1 envelope glycoprotein (Env) or engineered Envs, thus, large-scale expression and purification of isolated clones and characterization of purified soluble antibodies for neutralization breadth and potency were required, which was costly and time-consuming. Methods: Here, we developed a novel methodology for isolating HIV-1 bnmAbs based on antibody neutralization activity by displaying immune antibody libraries on target cell surface followed by sorting the cells by antibody neutralization ability to specific pseudotype virus. Results: After several rounds of sorting, a panel of human mAbs has been isolated from two ‘‘elite controllers’’ that can neutralize various isolates from clade B and clade C. Conclusion: We are currently measuring the neutralizing capability of these mAbs against different clades of virus, and expressing these mAbs as soluble form and will test them in a standardized TZM-bl neutralization assay to confirm the neutralization breadth and potency of isolated mAbs.