Immune Mechanisms Modulating The Development Of Breadth In The Antibody Repertoire Of HIV Infected Subjects

Abstract

Decrypting the dynamics of the interplay between diversification of the viral quasispecies and evolution of the antibody repertoire can improve our understanding of the immunological mechanisms mediating the development of antibody breadth during human immunodeficiency virus type 1 (HIV-1) infection. By isolating and characterizing of a panel of human monoclonal antibodies (mAbs) from two subjects who developed broadly neutralizing antibody responses during HIV-1 infection, I identified collections of mAbs that exhibited differential binding and neutralization specificities, and determined that a cooperative polyclonal process mediated by diverse antibodies with more limited breadth targeting multiple epitopes, could serve as an alternate route to achieving breadth of serum neutralizing activity against HIV-1. Utilizing next generation sequencing techniques, I was able to identify somatic variants related to antibodies I isolated from both subjects, and determined through functional studies that some of these somatic variants had achieved higher breadth of Env binding than the related isolated antibody.