Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines |
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Authors: | J-P?Carralot J?Probst I?Hoerr B?Scheel R?Teufel G?Jung H-G?Rammensee Email author" target="_blank">S?PascoloEmail author |
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Institution: | (1) CureVac GmbH, Paul Ehrlich Strasse 15, 72076 Tübingen, Germany;(2) Institute for Cell Biology, Department of Immunology, Auf der Morgenstelle 15, 72076 Tübingen, Germany;(3) Institute of Organic Chemistry, Auf der Morgenstelle 18, 72076 Tübingen, Germany |
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Abstract: | In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based
vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to
any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled
expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies).
We report here that injection of naked -globin untranslated region (UTR)-stabilized mRNA coding for
-galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy
primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application
of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the
administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the
requirement of antiviral, antibacterial or antitumor immunity.Received 14 June 2004; received after revision 19 July 2004; accepted 9 August 2004 |
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Keywords: | Vaccination Th1/Th2 cell rodent gene therapy messenger RNA GM-CSF |
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