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<i>In vivo</i> application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies
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2000
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Immune RegulationImmunologyImmunodominanceImmunologic MechanismAntigen ProcessingCd4 T Cell ResponsesImmune SystemImmunotherapyRna VaccinesCancer VaccinesAntibody EngineeringSpecific Cytotoxic TAllergyAutoimmunityT Cell ImmunityLacz GeneCell BiologyVaccinationRnase DegradationVaccine DesignCellular Immune ResponseMedicineViral Immunity
RNA vaccines can be produced in large quantities and share the advantages of DNA vaccines while avoiding the risk of genomic integration. The study aimed to evaluate the efficiency of RNA‑based vaccines encoding the model antigen beta‑galactosidase. RNA was transcribed, condensed with protamine, and administered to mice either naked, as a condensed complex, or liposome‑encapsulated. All preparations induced local protein expression, activated beta‑gal‑specific CTLs and IgG antibodies, and RNA‑induced CTLs were as effective as those from a DNA vector, demonstrating that both naked and protected RNA can elicit a specific immune response in vivo.
To study the efficiency of RNA-based vaccines, RNA coding for the model antigen beta-galactosidase (beta-gal) was transcribed in vitro from a lacZ gene flanked by stabilizing Xenopus laevis beta-globin 5' and 3' sequences and was protected from RNase degradation by condensation with the polycationic peptide protamine. The liposome-encapsulated condensed RNA-peptide complex, the condensed RNA-peptide complex without liposome or naked, unprotected RNA, was injected into BALB/c (H-2(d)) mice. All preparations led to protein expression in the local tissue, activation of L(d)-restricted specific cytotoxic T lymphocytes (CTL) and production of IgG antibodies reactive against beta-gal. RNA-triggered CTL were as efficient in the lysis of lacZ-transfected target cells as CTL triggered by a lacZ-DNA eukaryotic expression vector. Immunization with RNA transcribed from a cDNA library from the beta-gal-expressing cell line P13.1 again led to beta-gal-specific CTL and IgG induction. Thus, both naked and protected RNA can be used to elicit a specific immune response in vivo, whereby the protected RNA is stable in vitro for a longer period of time. RNA vaccines can be produced in high amounts and have the same major advantages as DNA vaccines but lack the potentially harmful effect of DNA integration into the genome.