VRC Home

Office of the Director
Key Personnel
Dr. Peter Kwong

Dr. Peter Kwong joined the Dale and Betty Bumpers Vaccine Research Center as chief of the Structural Biology Section in the Laboratory of Virology. Dr. Kwong comes to the Washington area from New York City, where he conducted research in the Department of Biochemistry and Molecular Biophysics at Columbia University.

Dr. Kwong's research specialty is structural biology. Specifically, he has studied the atomic-level structures of both the HIV protein, gp120, which resides on the outer surface of the virus as well as the structure of the primary HIV receptor, CD4. HIV uses gp120 to find and latch onto special CD4-containing immune cells in the first step of infection. Because of its exposed position on the outer surface of the virus, gp120 is the primary target of antibodies, the body's first line of defense against the invading virus. But, by mechanisms still not fully understood, gp120 is able to evade most of these antibodies.

Because of its central role in evading the immune system, many investigators had previously attempted to analyze the gp120 structure. However, these attempts were not successful due to masking of the gp120 molecule. Dr. Kwong and his research collaborators constructed altered forms of the gp120 protein until they found one that was suitable for analysis. By using X-ray crystallography, Dr. Kwong elucidated the atomic-level structure of gp120 in complex with the CD4 receptor and a neutralizing human antibody. The results of this seminal experiment and discovery were published in the journals Nature and Science in 1998.

Although structural information has not played a large role in vaccine development thus far, Dr. Kwong's research may change this. Since arriving at the VRC in 2001, Dr. Kwong and his research team have focused on three areas of investigation: 1) Unveiling mechanisms used by the HIV-1 envelope to evade the humoral immune response; 2) The characterization of antibodies that neutralize HIV-1, including their precise epitopes and mechanisms of neutralization; and 3) The design of envelope-based vaccine immunogens that elicit an effective antibody immune response against HIV-1.

The most dramatic advances have been in understanding mechanisms used by HIV-1 to disguise its surface, thereby evading the immune system's attack of neutralizing antibodies. These involve novel mechanisms of conformational masking and glycan shielding (published in the journal Nature in 2002 and 2003). The investigations of antibodies have also revealed novel mechanisms of binding, involving membrane interactions with the broadly neutralizing anti-HIV-1 antibody, 2F5, and of mimicry, involving antibody sulfation with the CD4i-class of gp120-reactive antibodies.

By studying the mechanisms gp120 uses to evade the immune system, Dr. Kwong and his team hope to find how to disable them and construct a modified HIV-1 envelope that will elicit an immune response against HIV. Conversely, by understanding how the rare select antibodies from HIV-1 infected individuals can neutralize HIV-1, Dr. Kwong and his team hope to understand how they might be efficiently re-elicited. The success of this research may lead to new strategies for developing vaccines against HIV as well as against other disease-causing viruses.

Dr. Kwong earned a bachelor's degree in chemistry and physics and a master's degree in biochemistry from the University of Chicago (at the precocious age of 20). He earned his second master's degree and his doctoral degree in biochemistry and molecular biophysics from Columbia University in New York.