A Novel Adjuvant for Improved Immunological Stimulation

Web Published:
6/9/2014
Description:

Princeton Docket # 14-3007

 

Researchers in the Department of Molecular Biology at Princeton University have isolated a mutant strain of Escherichia coli that is specifically more resistant to vancomycin than is its wild-type parent.  The resistance mutation in this strain alters an enzyme normally involved in LPS biosynthesis causing it to synthesize LPS molecules that are modified with peptidoglycan cell wall fragments (PG).  This altered LPS glycoform (LPS*) displays vancomycin-binding sites at the cell surface that act as extracellular decoys and that increase resistance by sequestering vancomycin.  Both LPS and PG are potent activators of immune responses, and they act via distinct mechanisms. The LPS* glycoform combines both these activators into one molecule. Hence, it is expected that LPS* may provide synergistic activation of immunity and provide a more potent immune response, an extended duration of immune response, or an altered type of immune response. Such properties of LPS* may be useful for commercial application of immune stimulants, such as vaccine adjuvants. 

The in vivo biosynthesis of LPS* has been determined and the chemical composition of LPS* has been elucidated.  Investigations to characterize the immunological response to LPS* and it’s derivatives are planned.

Advantages:

 

·         Boost intensity of immune response

 

·         Boost duration of immune reponse

 

·         Alter immune response

Applications:   

 

·         Immune stimulant

 

·         Improved vaccine adjuvant

 

Inventors

 

Thomas Silhavy is the Warner-Lambert Parke-Davis Professor of Molecular Biology at Princeton University.  Silhavy is best known for his work on protein secretion, membrane biogenesis, and signal transduction.  Using Escherichia coli as a model system, his lab was the first to isolate signal sequence mutations, to identify a component of cellular protein secretion machinery, and an integral membrane component of the outer membrane assembly machinery, and to identify and characterize a two-component regulatory system. 

 

Professor Silhavy received his BS in Pharmacy (summa cum laude, 1971) from Ferris State College and his MS (1974) and PhD (1975) in Biological Chemistry from Harvard University.  In recognition of his scientific accomplishments Silhavy was awarded an honorary Doctor of Sciences degree from his alma mater, Ferris State College (1982), was elected Fellow of the American Academy of Microbiology (1994), the American Association for the Advancement of Science (2004), and the American Academy of Arts and Sciences (2005), and he is a member of the National Academy of Sciences (2005) and an associate member of EMBO (2008).  In 1999 he received an NIH MERIT award, and he received the Novitski Prize for creativity from the Genetics Society of America in 2008.  His commitment to teaching is evidenced by the President’s Award for Distinguished Teaching at Princeton (1993), the Graduate Microbiology Teaching award from the American Society for Microbiology (2002), and the Graduate Advising Award at Princeton (2003).

Marcin Grabowicz, Post-Doctoral Researcher, obtained a Bachelor of Science with First Class Honors from the University of Adelaide, Australia, where he investigated prospective protein antigens for inclusion into a pneumococcal protein vaccine in the laboratory of Professor James C. Paton. He pursued his doctoral studies in Adelaide under the supervision of Associate Professor Renato Morona, investigating a key virulence protein of the pathogen Shigella. In 2010, Marcin joined the laboratory of Professor Thomas J. Silhavy at Princeton University and is carrying out research to understand the assembly of the Escherichia coli outer membrane.

David Kahne is Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. The Kahne Lab is interested in understanding the biogenesis of the cell envelope of Gram-negative bacteria, in particular peptidoglycan biosynthesis and outer membrane assembly. The assembly of this organellar membrane must be accomplished outside the cell in the absence of an obvious energy source. The research focuses on identifying and understanding the machinery necessary for proper assembly of this membrane barrier, as well as the mechanisms that lead to defects.

Intellectual Property Status

Patent protection is pending.

Princeton is seeking to identify appropriate partners for the further development and commercialization of this technology.

Contact

Laurie Tzodikov
Princeton University Office of Technology Licensing • (609) 258-7256•
tzodikov@princeton.edu

Laurie Bagley
Princeton University Office of Technology Licensing • (609) 258-5579•
lbagley@princeton.edu

 

 

 

 

Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
tzodikov@Princeton.EDU
Inventors:
Thomas Silhavy
Marcin Grabowicz
Daniel Kahne
Matthew Lebar
Dorothee Andres
Keywords:
anitbiotics
antibody
immunology
therapeutic
vaccines