Vaccine strategy relates to the engineering and creation of live-attenuated RSV vaccine candidates by shifting the position of one or more viral genes relative to the viral promoter

Available for licensing and commercial development is a patent estate and related biological materials for producing therapeutic or prophylactic vaccines against Respiratory Syncytial Virus (RSV).  The claimed vaccine strategy relates to the engineering and creation of live-attenuated RSV vaccine candidates by shifting the position of one or more viral genes relative to the viral promoter (aka promoter-proximal attenuation). The gene shifts can be constructed by insertion, deletion or rearrangement of genes or genome segments within the recombinant genome or antigenome. Viral replication can increase or decrease depending on the position of expressed viral gene and depending on the nature and degree of the positional shift.  Viral gene rearrangements are selected to maintain sufficient non-infectious replication of RSV while eliciting host anti-RSV immune responses.  Viral genes targeted for such rearrangement include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or genome segment.

 

One modification of particular interest is the placement of the G and F protective antigen genes in a promoter-proximal position for increased expression. The gene position-shifted RSV can be further manipulated by the addition of specific nucleotide and amino acid point mutations or host range restriction determinants to yield desired phenotypic and structural effects.

 

Applications:

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

 

Publications:

1. C Krempl et al.  Recombinant respiratory syncytial virus with the G and F genes shifted to the promoter-proximal positions.  J Virol.2002 Dec;76(23):11931-11942.  [PubMed abs]
2. Y Aloni, N Hay.  Attenuation may regulate gene expression in animal viruses and cells.  CRC Crit Rev Biochem. 1985;18(4):327-383.  [PubMed abs]

HHS Reference No. E-225-2000/0 --

• U.S. Patent No. 6,923,971 issued 02 Aug 2005;
• U.S. Patent Application No. 11/033,055 filed 10 Jan 2005;
• U.S. Patent Application No. 11/054,343 filed 08 Feb 2005;
• International Patent Application PCT/US2001/20107, which published as WO 2002/00693 on 03 Jan 2002 (expired);
• Australian Patent 2001268709;
• Brazilian Patent Application PI0112276-2;
• Canadian Patent Application 2413786;
• Chinese Patent Application 01814362.8;
• European Patent Application 01946696.0;
• Israeli Patent Application 153530;
• Japanese Patent Application 10-2002-505815;
• Korean Patent Application 10-2002-7017577; and
• Mexican Patent Application 2002-012818.

 

Inventors:

Christine D. Krempl, Peter L. Collins, Brian R. Murphy, Ursula Buchholz, Stephen S. Whitehead (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 live attenuated vaccines.  Please contact Michael Piziali at 301-451-3527 for more information.