The Use of HIV Genetics for the Development and Evaluation of AIDS Vaccines and Cure Research

HIV sequence diversity has presented a major hurdle for the development of both AIDS vaccines and effective therapies. On the vaccine side, the enormous global diversity that has evolved makes development of immunogens, presenting antigens that would mimic a large fraction of viruses that a vaccinee might encounter, a truly daunting task. The ability of the virus to evolve structures that fail to bind antiviral drugs while retaining viability, however, has been largely overcome by the simultaneous use of multiple drugs. Such combination antiretroviral therapies (cART) decrease virus replication to such low levels that the likelihood that a virus could evolve the multiple resistance mutations required to resist each drug is very small. However, cART is incapable of acting on viral genomes that are latent within an infected cell or that are present in anatomical or cellular reservoirs that restrict drug penetration.

We are using viral genetics to interpret the impact of HIV vaccines on breakthrough infections that have occurred in large clinical trials (the STEP and RV144 trials), and to design a new type of vaccine based on genetically conserved regions of the virus (CE, or conserved elements vaccines). We are also using viral genetics to identify virus reservoirs in cART treated subjects, as well as attempting to develop a new approach to treating viral infections through acceleration of viral mutation rates to the point that the viral population can no longer survive. These topics will be reviewed and recent data from our group that describes the status of each approach will be described.

Dr. James Mullins, Professor of Microbiology and of Medicine, University of Washington

Dr. Mullins obtained his Ph.D. in Cell Biology and Biochemistry from the University of Minnesota in 1978. He did postdoctoral work at the California Institute of Technology before becoming Assistant then Associate Professor at the Harvard University School of Public Health. In 1989 he moved to Stanford University as Professor and was Chairman of the Department of Microbiology and Immunology from 1991 until his move to the University of Washington in 1994, where he is on the faculty of the Departments of Microbiology, Medicine, and Laboratory Medicine. He served as Chair of Microbiology from 1997-2002.

The Mullins lab uses the techniques of molecular, computational, and virus biology to provide basic insights into the HIV-human host relationship in an effort to assist the fight to stop the AIDS pandemic. They use a variety of techniques to understand the implications of HIV's extraordinary genetic diversity for the pathogenesis of AIDS, with the intention of applying this information to the development of more effective therapies and vaccines. These techniques include virology and the molecular biological and statistical analysis of nucleotide sequences.