Novel MVA Mutant eliciting enhanced T cell Memory

Reference Number TO 01-00440

 

The Challenge

 

Absence of pathogenicity for humans, avirulence even in immunocompromized hosts, high-level expression of foreign antigens and strong adjuvant effect make recombinant MVA (rMVA) an ideal vector for both prophylactic and therapeutic vaccination.

Interleukin 1b (IL1b ) is an important regulator of inflammatory responses and contributes to host immune defense against infection. MVA and other orthopoxviruses encode a viral soluble IL1b -receptor (IL1b R), which modulates the acute-phase host response to infection and might influence the induction of immune responses against virus-associated antigens. Due to conflicting data from experiments after deletion of the IL1b R gene in vaccinia virus, the role of MVA IL1b R gene in modulation of MVA life cycle and host response to MVA is still unclear.

 

 

	Analysis of memory response in HHD mice. Source: WO 05/030971

 

The Technology

 

IL1b R deficient MVA (MVA-D IL1b R) shows the same growth characteristics as wtMVA on chicken embryonic fibroblast cells. As shown by intranasal infection of mice with high doses of MVA-D IL1b R, the mutant virus is as safe as wtMVA. After vaccination of mice, MVA-D IL1b R or wtMVA induced similar acute-phase immune responses. Importantly, in the memory phase, MVA-D IL1b R elicits significantly higher MVA-specific total CD8⁺ and peptide-specific T-cell responses. Moreover, 4–6 months after vaccination, MVA-D IL1b R provided higher levels of protection against lethal challenge infection with virulent vaccinia virus strain Western Reserve compared with wtMVA. These data suggest that deletion of the viral IL1b R gene may amplify the virus-specific CD8⁺ memory T-cell response and duration of protective immunity obtained after MVA vaccination.

 

Commercial Benefit

 

MVA-D IL1b R induces high level T cell memory and can be used as efficient vector for vaccines against pathologic microorganisms, viruses and tumors.

 

Patent situation

 

Patent applications are pending in AU, BR, CN, EP, IN, and US.

 

Commercial Opportunity

 

The technology is available for exclusive and non-exclusive licensing. Parties interested in collaborative research and development are highly welcomed.

 

Relevant Publication

 

Staib et al. (2005), J. Gen. Virol. 86, 1997-2006.

The novel MVA mutant is currently used as vector in murine vaccination studies using MVA-nef as rMVA.

 

 

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Kontakt:

Dr. Hubert Müller
Technology Manager
Ascenion GmbH

T: +49 (0)89 318814-32
F: +49 (0)89 318814-20
E: mueller(at)ascenion.de