Abstract Book 2010 - CIMT Annual Meeting

114 Lehmann | Enhancing immunity & adjuvants
Modified vaccinia virus Ankara (MVA) - a safe vector virus
and an adjuvant system for immunotherapy
Michael H. Lehmann 1 , Ulrich Kalinke 2 , Gerd Sutter 1
1 Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München,
80539 Munich, Germany
2 TWINCORE, Centre of Experimental and Clinical Infection Research, 30625 Hannover, Germany
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Modified vaccinia virus Ankara (MVA) is a highly
attenuated strain of vaccinia virus (VACV) being
generated through serial passage in chicken
embryo fibroblast cells [1]. Until 1988, MVA was
used for safer vaccination against smallpox and has
been administered to more than 100 000 humans
without documentation of the severe adverse reactions
associated with the use of conventional VACV
vaccines. Analysis of the MVA genome revealed that
during the attenuation process the virus had lost a
substantial amount of genetic information including
many viral genes regulating virus-host interaction.
In consequence, MVA is unable to propagate
in human and many other mammalian cells but
can efficiently express viral and recombinant genes
[2]. This phenotype strongly supported its use as
viral vector and, by today, a variety of recombinant
MVA vaccines are undergoing clinical testing in
immune prophylaxis and immune therapy against
infectious diseases and cancer.
Here, we investigated the immune stimulatory properties
of MVA. Surprisingly, MVA but not other
VACV strains induced expression of type I IFNs [3].
We detected IFN-beta both in human monocytic
cells and in the lungs of mice intranasally infected
with MVA. Additionally, infection of human cells
or mice with MVA but not with other VACV strains
efficiently induced the expression of several chemokines
(CCL2, CCL3, CCL4, CXCL1, CXCL10),
which led to the fast attraction of leukocytes including
monocytes, neutrophils, CD4+ and CD8+
lymphocytes to the site of infection [4]. Since active
immigration of immune cells to the site of immunization
is a prerequisite for induction of an effective
immune response, MVA vaccines naturally comprise
this hallmark of a potent vaccine adjuvant.
In summary, the properties making MVA an ideal
vector for immunotherapeutic protocols are (i) its
clinical safety as replication deficient virus, (ii) its
ability to easily transfer and express foreign genetic
material in target cells of choice and, (iii) its capacity
to activate type I interferons, chemokines and
thereby a rapid immigration of leukocytes.
References
[1] A. Mayr, E. Munz, Veränderungen von Vaccinevirus durch
Dauerpassagen auf Hühnerembryofibroblasten-Kulturen,
Zentralbl. Bakteriol. Orig. A 195 (1964) 24-35.
[2] G. Sutter, B. Moss, Nonreplicating vaccinia vector efficient
ly expresses recombinant genes, Proc. Natl. Acad. Sci. USA
89 (1992) 10847-10851.
[3] Z. Waibler, M. Anzaghe, H. Ludwig, S. Akira, S. Weiss, G.
Sutter, U. Kalinke, Modified vaccinia virus Ankara induces
Toll-like receptor-independent type I interferon responses, J.
Virol. 81 (2007) 12102-12110.
[4] M.H. Lehmann, W. Kastenmuller, J.D. Kandemir, F. Brandt,
Y. Suezer, G. Sutter, Modified vaccinia virus ankara triggers
chemotaxis of monocytes and early respiratory immigration
of leukocytes by induction of CCL2 expression, J. Virol. 83
2009) 2540-2552.