Novel MVA mutant eliciting enhanced T cell memory

Reference Number TO 01-00440

 

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 (IL1bR), 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 IL1bR gene in vaccinia virus, the role of MVA IL1bR gene in modulation of MVA life cycle and host response to MVA is still unclear. 

  

 

Technology 

IL1bR deficient MVA (MVA-DIL1bR) shows the same growth characteristics as wtMVA on chicken embryonic fibroblast cells. As shown by intranasal infection of mice with high doses of MVA-DIL1bR, the mutant virus is as safe as wtMVA. After vaccination of mice, MVA-DIL1bR or wtMVA induced similar acute-phase immune responses. Importantly, in the memory phase, MVA-DIL1bR elicits significantly higher MVA-specific total CD8+ and peptide-specific T-cell responses. Moreover, 4–6 months after vaccination, MVA-DIL1bR 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 IL1bR gene may amplify the virus-specific CD8+ memory T-cell response and duration of protective immunity obtained after MVA vaccination.

 

Commercial Benefit and Opportunity

The work so far recommends deletion of the viral IL1bR gene as a first step towards the development of a new generation of MVA-based vaccines. The improved vaccine properties of MVA-DIL1bR is particularly promising, since it demonstrates the possibility of obtaining more efficacious MVA vaccines through rational genetic engineering.
The technology is available for non-exclusive licensing. Parties interested in collaborative research and development are highly welcomed. 

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

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

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

 

 

 

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Kontakt:

Hubert Müller, Ph.D.
Technology Manager
Ascenion GmbH

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