Development of a Novel High Throughput Assay to Measure Cell-Infection with Vaccinia Strains Expressing Reporter Genes
Description of Invention:
Critical to developing a vaccine against viral infections is an assay to measure the neutralizing antibody present in blood of vaccine recipients. The currently available tests are labor intensive and require 5-6 days to complete. The inventors have designed a high throughput vaccinia neutralization assay, which offers several advantages over the assays that are currently used. It is completed in as little as 24 hours, it is sensitive, highly reproducible, requires only 50 µl of plasma and uses automated readout. This assay is based on the use of recombinant vaccinia virus (vSC56) expressing a bacterial gene coding for the enzyme b-galactosidase (b-Gal) under the control of a synthetic early/late promotor. Another recombinant virus expressing an inducible reporter gene (Luciferase) is also being tested in neutralization assay. These assays may be of value in the clinical trials of new smallpox vaccines, for evaluations of new vaccinia immunoglobulin (VIG) and anti-viral agents under development. The technology itself may be adapted for construction of neutralization assays for other viruses and intracellular pathogens.
Patent Status:
DHHS Reference No. E-300-2002/0 --
U.S. Provisional Patent Application 60/429,767 filed 27 Nov 2002
PCT Application No. PCT/US03/37677 filed 24 Nov 2003, which published as WO 2004/053454 on 24 Jun 2004
U.S. Patent Application No. 10/536,860 filed 06 Jan 2006
Relevant Publication:
J Manischewitz, L. King, NA Bleckwenn, J Shiloach, R Taffs, M Merchlinsky, N Eller, MG Mikolajczyk. DJ Clanton, T Monath, RA Weltzin, DE Scott, H Golding. Development of a novel vaccinia-neutralization assay based on reporter-gene expression. J Infect Dis. 2003 Aug 1;188(3):440-448. [PubMed abs]
Y Edghill-Smith, D Venzon, T Karpova, J McNally, J Nacsa, W-P Tsai, E Tryniszewska, M Moniuszko, J Manischewitz, LR King, S J Snodgrass, J Parrish, P Markham, MG Lewis, M Sowers, D Martin, JA Berzofsky, IM Belyakov, B Moss, J Tartaglia, M Bray, V Hirsch, H Golding, G Franchini. Modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised macques. J Infect Dis. 2003 Oct 15;188(8):1181-1191. [PubMed abs]
JC Goldsmith, N Eller, M Mikolajczyk, J Manischewitz, H Golding, D Scott. Intravenous immunoglobulin products contain neutralizing antibodies to vaccinia. Vox Sang. 2004 Feb;86(2):125-129. [PubMed abs]
Y Edghill-Smith, M Bray, CA Whitehouse, D Miller, E Mucker, J Manischewitz, LR King, M Robert-Guroff, A Hryniewiecz, D Venzon, C Meseda, J Weir, A Nalca, J Wells, MG Lewis, J Huggins, SH Zwiers, H Golding, G Franchini. Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge. J Infect Dis. 2005 Feb 1;191(3):372-381. [PubMed abs]
Y Edghill-Smith, H Golding, J Manischewitz, LR King, D Scott, M Bray, A Nalca, JW Hooper, CA Whitehouse, KA Reimann, G Franchini. Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus. Nat Med. 2005 Jul;11(7):740-747. [PubMed abs]
CA Meseda, AD Garcia, A Kumar, AE Mayer, J Manischewits, LR King, H Golding, M Merchlinsky, J Weir. Enhanced immunogenicity and protective effect conferred by vaccination with combinations of modified vaccinia Ankara and licensed smallpox vaccine Dryvax in a mouse model. Virology. 2005 Sep 1;339(2):164-175. [PubMed abs]
KH Waibel, H Golding, J Manischewitz, LR King, M Tuchscherer, RL Topolski, DS Walsh. Clinical and immunological comparison of smallpox vaccination administered to the outer versus the inner upper arms of vaccinia-naïve adults. Clin Infect Dis. 2006 Feb 15;42(4):e16-20. [PubMed abs]
JM Heraud, Y Edghill-Smith, V Ayala, I Kalisz, J Parrino, VS Kalyanaraman, J Manischewitz, LR King, A Hryniewicz, CJ Trindade, M Hassett, W-P Tsai, D Venzon, A Nalca, M Vaccari, P Silvera, M Bray, BS Graham, H Golding, JW Hooper, G Franchini. Subunit recombinant vaccine protects against monkeypox . J.Immunol. 2006 Aug 15;177(4):2552-2564. [PubMed abs]
VL Kan, J Manischewitz, LR King, H Golding. Durable neutralizing antibodies after remote smallpox vaccination among adults with and without HIV infection. AIDS. 2007 Feb 19;21(4):521-524. [PubMed abs]
Licensing Status: Available for licensing.
Collaborative Research Opportunity:
The CBER/FDA Laboratory of Retrovirus Research is seeking statements of capability or interest from parties interested in collaborative research to further develop or evaluate novel anti-vaccinia agents including monoclonal antibodies and vaccines. Please contact Hana Golding at Tel: 301-827-0784 or E-mail: hana.golding@fda.hhs.gov for more information.
For Additional Information Please Contact: Peter A. Soukas J.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4646
Email: soukasp@mail.nih.gov
Fax: (301) 402-0220
