Available for licensing and commercial development is a patent estate and related biological materials for making human-bovine chimeric virus particles for formulating live attenuated vaccines against human respiratory syncytial virus (RSV). Chimeric human-bovine RSVs are recombinantly engineered to incorporate nucleotide sequences from both human and bovine RSV strains and produce infectious, chimeric viruses that elicit anti-RSV immunological responses in humans and non-human primates. The chimeras incorporate partial or complete human or bovine RSV background genomes with one or more recombinantly integrated heterologous genes or genome segments of a different RSV strain.

Heterologous genes of interest for making chimeric recombinants include NS1, NS2, N, P, M, SH glycoprotein (or an immunogenic domain or epitope thereof), M2(ORF1), M2(ORF2), L, F or G genes or a genome segment including a protein or portion thereof or alternatively a leader, trailer or intergenic region of the RSV genome, or a segment thereof.  A variety of additional mutations and nucleotide modifications are provided within the human-bovine chimeric RSV of the invention to yield desired phenotypic and structural effects. Exemplary human-bovine chimeric RSV of the invention incorporate a chimeric RSV genome or antigenome comprising both human and bovine polynucleotide sequences, as well as a major nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P), a large polymerase protein (L), and a RNA polymerase elongation factor. Additional RSV proteins may be included in various combinations to provide a range of infectious subviral particles up to a complete viral particle or a viral particle containing supernumerary proteins, antigenic determinants or other additional components.

Applications:

• Infectious Disease - Respiratory Syncytial Virus
• Vaccines
• Therapeutics
• Prophylactics
• Childhood Vaccines

Publications:

1. UJ Buchholz et al. Chimeric bovine respiratory syncytial virus with glycoprotein gene substitutions from human respiratory syncytial virus (HRSV): effects on host range and evaluation as a live-attenuated HRSV vaccine. J Virol. 2000 Feb;74(3):1187-1199.  [PubMed abs]
2. A Karger et al. Recombinant bovine respiratory syncytial virus with deletions of the G or SH genes: G and F proteins bind heparin. J Gen Virol. 2001 Mar;82(Pt 3):631-640.  [PubMed abs]
3. UJ Buchholz et al. Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. J Virol. 1999 Jan;73(1):251-259.  [PubMed abs]

HHS Reference No. E-178-1999/0 --

• International Patent Application PCT/US00/17755, which published as WO 2001/04335 on 09 Jan 2001 (expired);
• Australian Patent 784216;
• Chinese Patent 00810119.1;
• Canadian Patent Application 2378552;
• European Patent Application 00941756.9;
• Israeli Patent Application 147447;
• Japanese Patent Application 2001-509539;
• Korean Patent Application 10-2002-7000318;
• Mexican Patent Application 2002-000220;
• Brazilian Patent Application PI0013195-4; and
• Chinese Patent Application 200710167112.6

HHS Reference No. E-178-1999/1 --

• U.S. Patent Application No. 11/097,946 filed 31 Mar 2005

HHS Reference No. E-178-1999/2 --

• U.S. Patent Application No. 10/704,116 filed 07 Nov 2003

Inventors:

Ursula Buchholz, Peter L. Collins, Brian R. Murphy, Stephen S. Whitehead, Christine D. Krempl (NIAID)

Licensees Sought:

Available for licensing.

Collaborative Research Opportunity:

The NIAID Office of Technology Development is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize attenuated live vaccines against respiratory syncytial virus (RSV).  Please contact Barry Buchbinder at 301-594-1696 for more information.