Date

August 2012

Document Type

Dissertation

Degree Name

Ph.D.

Department

Dept. of Molecular Microbiology and Immunology

Institution

Oregon Health & Science University

Abstract

Considerable progress has been made in recent years, reinvigorating the HIV NAb field. Nevertheless, important questions remain concerning Env structure that can lead to the development of an immunogen that can elicit hNAbs. In this regard, recent evidence demonstrates that sequential immunization with HIV-1 Envs that evolved in a macaque infected with pathogenic SHIV leads to broadening of NAbs in rabbits, and that these NAbs are more similar to the NAbs generated durig SHIV infection (253). The aim of the work presented here is to extend these data using human-derived envs. I hypothesize that envs derived from the viral quasispecies of HIV-infected subjects that develop broad NAbs contribute to the development of this response; moreover, these Env variants develop particular immunogenic features that drive Env-specific B cells down a particular maturation pathway as they diverge over the course of infection, leading to broad NAbs. In Chapter Two, I explore the using a rational method

Identifier

doi:10.6083/M4CV4FRM

School

School of Medicine

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