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Over the past decade our understanding of innate immunity has grown exponentially. This occurred with the discovery of
TOLL-like receptors (TLRs) followed by a set of intracellular pattern recognition receptors termed NODS or NOD-like
receptors (NLRs). For many years, it has been known that the most potent immune adjuvants have been derived from microbial
products, followed by an understanding that these products enhanced antigen presentation by increasing T cell costimulation
through an up regulation of various APC costimulatory molecules, especially CD86. Vaccines components that were not entirely
?clean? always appeared to be more immunogenic, and Charles Janeway termed this the ?immunologist?s dirty little secret?. We
now know that a majority of these vaccine adjuvants are some type of TLR or NLR ligand and/or stimulate APCs indirectly or
directly through these pathways. We have found that the Neisserial major outer membrane protein PorB, has significant immune
activating activity, can act as a potent vaccine adjuvant and that the mechanism of this activity is mediated by its interaction with
TLR2. PorB can enhance immune responses to both T-cell independent or dependent antigens that are associated with protection
from microbial pathogens, including encapsulated bacteria or Francisella tularensis. Experiments are ongoing comparing the
adjuvant activity of PorB to other adjuvants that are currently being used or are being developed to better understand their effects,
which may allow for a more effective use of these adjuvants in future vaccines.
Lee M. Wetzler is currently a Professor of Medicine and an Associate Professor of Microbiology at the Boston University School of Medicine and
an Attending Physician at the Boston Medical Center. He has a long standing interest in vaccinology and vaccine adjuvants since his postdoctoral
fellowship at the Rockefeller University in NY, in the laboratory of Dr. Emil Gotschlich, the original developer of the meningococcal polysaccharide
vaccines. He did his residency at the University of Michigan, his Infectious Diseases fellowship at the Boston University School of Medicine and has
been on faculty at this institution for almost two decades.
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