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Veterinary
Medicine
Guy H. Palmer
Genomics and Proteomics in Vaccine Development
Dr.
Guy Palmer and his colleagues are using genomics and
proteomics to identify new targets for vaccine development
with the goal of preventing infectious diseases.
| Key
to vaccine development is the identification of specific
sites within microbial proteins, termed epitopes,
that bind surface receptors on lymphocytes and stimulate
their proliferation. Traditional approaches to epitope
identification were based on either knowing the function
of the microbial protein, such as a ligand for binding
to host cells, or its location within the microbe,
for example, on the outer membrane surface. |
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While
these approaches resulted in vaccines against numerous
infectious agents, many important pathogens of animals
and humans remain uncontrolled due to poor vaccine efficacy.
A proteomic approach, however, can work in “reverse”— that
is the responding lymphocyte or antibody secreted by
the lymphocyte from an immune animal is used to select
the pathogen epitope without bias as to its function
or location. While this strategy itself is not new, it
is the availability of linked genomics and proteomics
that makes it technically feasible.
CD4+
T lymphocytes, cells that help B lymphocytes make antibody
to bind the pathogen and that activate phagocytic cells
to engulf the antibody-coated pathogen, bind to only
a small stretch of the protein, approximately 10-20 amino
acids. To search for this “needle in the haystack” among
the 1 million or so amino acids in a bacterium, the full
set of proteins are separated by molecular size and then
tested for stimulation of T lymphocytes from immune animals.
Those that stimulate T cell proliferation, still an unknown
mixture, are characterized by trypsin digestion followed
by mass spectrometry. The key to actually identifying
the proteins is to map these actual tryptic fragments
back to those predicted by analysis of the complete genome
sequence of the bacterium. The identified protein or
proteins can then be tested as a vaccine to confirm that
the predicted T cell response is induced.
Implementing
this strategy requires interdisciplinary expertise in
microbial structure, immunology, genomics, and proteomics.
At Washington State University, Dr. Palmer, immunologist
Dr. Wendy Brown, molecular genomicist Dr. Kelly Brayton,
and mass spectroscopy expert Dr. Bill Siems are using
this approach in vaccine development against the blood-borne
animal pathogen Anaplasma marginale. In addition to addressing
a need for a vaccine against this specific animal pathogen,
this research effort is leading new approaches to improve
the safety and efficacy of vaccines, including agents
at risk for use as bioterrorism agents.
Contact
Information
Guy H. Palmer, D.V.M., Ph.D.
Professor
Veterinary Microbiology and Pathology
Diplomate, American College of Veterinary Pathologists
Washington State University
PO Box 647040
Pullman, WA 99164-7040
Telephone:
509-335-6033
Fax: 509-335-8529
E-mail: gpalmer@vetmed.wsu.edu
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