Recombinant Baculoviruses Containing Inserts of the Major Structural Genes (vp1) of the Human Polyomaviruses JCV and BKV


The development of sensitive and specific tests for JC virus and BK virus activity may provide tools essential in the steps required to find a treatment for these fatal infections. This invention describes a Recombinant Vpl protein (rVp1) that can be used 1) as an antigen source for ELISA assays 2) for studies of viral proteins in cells and 3) for the self assembly of icosahedral particles encapsidating DNA [gene expression of choice in range of up to 5.1kb size gene].

rVp1 can be utilized in ELISA assays to detect both JCV and BKV antibodies. The JCV and BKV rVp1 proteins may serve as antigens for the production of useful anti-sera and monoclonal-antibodies for polyomavirus research, as well as for the detection of existing and/or changing levels of antibodies in human sera by way of ELISA assays. Such ELISA studies allow for tracking of the spread and/or reactivation of polyomavirus infections in the human population, of special importance for individuals at high risk of polyomavirus associated pathologies. The rVp1s eliminate the need to produce infectious, native polyomavirus virions as antigens for such work.

The rVp1 proteins may also be utilized as vector delivery systems. The rVp1 proteins self-assemble into Virus-Like Particles (VLPs) which can be dissociated, reconstituted in the presence of exogenous DNA (that is non-specifically encapsidated), and then internalized through cell membranes that native virions normally cross.

Potential Commercial Applications: Competitive Advantages:
  • JCV or BKV antigens useful for polyomavirus research
  • ELISA studies for individuals at high risk of polyomavirus associated pathologies
  • Vector Delivery systems
 


Development Stage:
ELISA is fully developed and materials are available for licensing.

Inventors:

Eugene Major (NINDS)  ➽ more inventions...

Peter Jensen (NINDS)  ➽ more inventions...


Intellectual Property:
Research Material -- patent protection is not being pursued for this technology

Publications:
C Goldmann et al. Molecular cloning and expression of major structural protein VP1 of the human polyomavirus JC virus: formation of virus-like particles useful for immunological and therapeutic studies. J Virol 1999 May;73(5):4465-4469. PubMed abs
RS Hamilton et al. Comparison of antibody titers determined by hemagglutination inhibition and enzyme immunoassay for JC virus and BK virus. J Clin Microbiol. 2000 Jan;38(1):105-109. PubMed abs
P Lenz et al. Papillomavirus-like particles induce acute activation of dendritic cells. J Immunol. 2001 May 1;166(9):5346-5355. PubMed abs
DL Bohl et al. Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia. Am J Transplant. 2005 Sep;5(9):2213-2221. PubMed abs
EO Major and P Matsumura. Human embryonic kidney cells: stable transformation with an origin-defective simian virus 40 DNA and use as hosts for human papovavirus replication. Mol Cell Biol. 1984 Feb;4(2):379-382. PubMed abs
EO Major et al. Establishment of a line of human fetal glial cells that supports JC virus multiplication. Proc Natl Acad Sci USA. 1985 Feb;82(4):1257-1261. PubMed abs

Collaboration Opportunity:

The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize treatment and prevention of polyomavirus infections in immunocompromised patients. Please contact Melissa Maderia, Ph.D., at maderiam@mail.nih.gov for more information.


Licensing Contact:
Susan Ano, Ph.D.
Email: susan.ano@nih.gov
Phone: 301-435-5515

OTT Reference No: E-216-2006/0
Updated: Aug 1, 2007