This technology describes a method that increases the ability of paramyxoviruses to encode a large foreign antigen for development of vaccines.
Recombinant paramyxoviruses encoding small foreign antigens have been successful at eliciting specific cellular and immune responses and some have also been used as oncolytic viruses. Paramyxoviruses are single stranded RNA viruses that have a single promoter at their 3’ end. Because of the single promoter the expression level of the viral genes are affected by the proximity to the promoter. Thus, genes closer to the promoter are highly transcribed while genes that are further away have a lower level of transcription.
To overcome the limitation of paramyxovirus to encode large foreign antigens. Dr. Palese and colleagues at the Icahn School of Medicine at Mount Sinai have split the genome of a paramyxovirus representative, Newcastle Disease Virus (NDV) into two segments. By adding a second promoter the ability to include larger foreign antigens by paramyxoviruses has been significantly increased to at least ~200kDa the size of the SARS coronavirus Spike protein.
Current Development Status
- The invention has been enabled in Newcastle Disease Virus by Dr. Palese and colleagues and has also been demonstrated in another member of the paramyxoviridae family, measles
Applications
- Generation of attenuated vaccines
Advantages
Paramyxoviruses offer many advantages over other viruses:
- Single stranded RNA virus – no risk of integration
NDV-specific:
- Lack of herd immunity
- Non-pathogenic in humans – unable to antagonize the antiviral state in mammals
- Demonstrated efficacy of rNDV vaccines in other models
Publications
- Gao et al. “Expression of transgenes from Newcastle Disease Virus with a segmented genome.” J Virol. 2008, 82(6):2692
- Takeda et al. “Generation of Measles Virus with a Segmented RNA Genome.” J Virol. May 2006, 80(9): 4242–4248
Patent Status
- Canadian Application 2,477,037 filed February 21, 2003
- Status: Issued. CA Patent No. 2,477,037
- EPC Application EP0723641 filed February 21, 2003
- Status: Published. EPC Publication No. EP1485488
- Australian Application 2003230559 filed February 21, 2003
- Status: Issued. AU Patent No. 2003230559
- US Utility Application 10/505,613 filed May 17, 2005
- Status: Issued. US Patent No. 8,709,442
- US Continuation Application 14/203,743 filed March 11, 2014
- Status: Published. US Publication No. 2014-0363878
Contact
Alan Belicha, PhD
Business Development Analyst
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: 646.605.7306