SBRI - Research: Scientists

Mission
The goal of Dr. Stamatatos’ work is to develop a safe and effective vaccine to combat the spread of HIV. To achieve this goal, he and his lab collaborate with several groups, both in academia and industry, throughout the United States.

Research
Dr. Stamatatos and his researchers examine how the phenotype of the human immunodeficiency virus (HIV) is affected by the structure of its Envelope glycoprotein. They are particularly interested in understanding how variations in amino acid sequence and glycosylation-patters of the viral envelope affect the interaction of this protein with receptor molecules on the target cell surfaces and regulate the efficiency of viral entry and transmission.

They are designing novel HIV Envelope-based immunogens to elicit potent and broad neutralizing antibody responses. One approach they are investigating is the introduction of specific modifications in the Envelope to increase the exposure of neutralization epitopes that are common among the various HIV strains. They compare the immunogenicity of these modified immunogens to that of the corresponding unmodified immunogens and they identify those that elicit the most promising antibody responses. The selected immunogens are optimized and re-tested in animals. Through several rounds of this iteration process, it is hoped that they will identify immunogens that would reproducible elicit the desired neutralizing antibody responses against HIV.

Dr. Stamatatos through various collaborations is also testing different approaches to elicit cross-neutralizing antibody responses against HIV. One of these approaches, which is pioneered by Drs. Baker and Schief (UW), is to use computational design to create proteins expressing known HIV neutralization epitopes. The hope is to re-create the HIV epitope in its native conformation on a non-HIV backbone, and thus focus the immune response to that particular epitope.

Dr. Stamatatos is also investigating the development of neutralizing antibody responses during natural HIV infection and how it relates to viral evolution. His group is identifying factors that may be conducive to the development of such responses, and plans to use this information to design more effective vaccines against HIV.

Themes
* HIV envelope structure/function relationship
* HIV transmission and pathogenesis

Accomplishments
*	Designed modified HIV envelope-based vaccines that elicit neutralizing antibodies against clinical HIV isolates
*	Demonstrated that this vaccine protects macaques from disease development

Collaborations
     * University of Washington
     * Fred Hutchinson Cancer Research Center
     * California Institute of Technology
     * Washington National Primate Research Center
     * Novartis, Vaccines and Diagnostics
     * Southwest Foundation for Biomedical Research

Dr. Stamatatos’ research is currently supported by the National Institutes of Health (NIH)
and the Bill & Melinda Gates Foundation.