August 2012

Document Type


Degree Name



Dept. of Molecular Microbiology and Immunology


Oregon Health & Science University


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




School of Medicine



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.