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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. |