Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines.
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 beta-globin untranslated region (UTR)-stabilized mRNA coding for beta-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.
Carralot
J-P
JP
CureVac GmbH, Paul Ehrlich Strasse 15, 72076 Tübingen, Germany.
Probst
J
J
Hoerr
I
I
Scheel
B
B
Teufel
R
R
Jung
G
G
Rammensee
H-G
HG
Pascolo
S
S
D000818:Animals; D000941:Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005914:Globins / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007267:Injections; D051379:Mice; D008807:Mice, Inbred BALB C; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D014612:Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D000941:Antigens; D016207:Cytokines; D012333:RNA, Messenger; D014612:Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005914:Globins; D001616:beta-Galactosidase