DNA and RNA-based vaccines: principles, progress and prospects

Leitner, Wolfgang W.; Han, Yangyang; Restifo, Nicholas P.

doi:10.1016/s0264-410x(99)00271-6

Cited by 345 publications

(236 citation statements)

References 135 publications

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“…9,26,27 The replicase also produces 5ʹ-triphosphate dsRNA of non-viral host cell RNA templates. 28 The RNA transcripts signal innate immunity through RNA sensing by Toll-like receptor 3 (TLR3), TLR7, TLR8, MDA-5, RIG-I and protein kinase R for a type I IFN response.…”

Section: Discussionmentioning

confidence: 99%

Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing human papilloma virus E6 and E7 antigens

Wall

Ljungberg

et al. 2018

OncoImmunology

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Cervical cancer develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7. Our group pioneered a recombinant viral vector system based on Semliki Forest virus (SFV) for vaccination against cervical cancer. The most striking benefit of this alphavirus vector-based vaccine platform is its high potency. DNA vaccines on the other hand, have a major advantage with respect to ease of production. In this study, the benefits associated with both SFV-based vaccines and DNA vaccines were combined with the development of a DNA-launched RNA replicon (DREP) vaccine targeting cervical cancer. Using intradermal delivery followed by electroporation, we demonstrated that DREP encoding for E6,7 (DREP-E6,7) induced effective, therapeutic antitumor immunity. While immunizations with a conventional DNA vaccine did not prevent tumor outgrowth, immunization with a 200-fold lower equimolar dose of DREP (0.05 µg of DREP) resulted in approximately 85% of tumor-free mice. To overcome the safety concern of potential malignant transformation at the vaccination site, we evaluated the anti-tumor effect of a DREP vaccine encoding a shuffled version of E7 (DREP-E7sh). DREP-E7sh delayed tumor growth yet not to the same extent as DREP-E6,7. In addition, inclusion of a helper cassette and an ER targeting signal (sigHelp) did not significantly further enhance the suppression of tumor outgrowth in the long term, albeit exhibiting better tumor control early after immunization. Collectively, this study points towards the clinical evaluation of DREP encoding HPV antigens as a potent immunotherapy for patients with HPV16 (pre)-malignancies.

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Section: Discussionmentioning

confidence: 99%

Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing human papilloma virus E6 and E7 antigens

Wall

Ljungberg

et al. 2018

OncoImmunology

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“…This might be due to the production of interferon molecules in vivo in response to dsRNA formation [20]. Since conventional virus vaccine is known to elicit poor CMI response, we have not evaluated in these studies.…”

Section: Discussionmentioning

confidence: 99%

Self Replicating Gene Vaccine Carrying P1-2A Gene of FMDV Serotype O and its Effects on the Immune Responses of Cattle

et al. 2011

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DNA vaccines are considered as alternatives to live attenuated ones for those diseases like foot-and-mouth disease (FMD) where the production and application of live vaccines have been found unsuccessful. However, stability of DNA and the quantity of antigen expressed are the major limitation with naked DNA vaccines. To address these issues self replicating gene vaccine construct was made for foot-and-mouth disease virus (FMDV) type 'O' and studied. The vector for vaccine construct, designated as pSinCMVVac carried CMV promoter and Poly(A) signal sequences at 5 0 and 3 0 end of Sindbis replicase gene respectively. Gene for structural protein precursor (P1-2A) of FMDV serotype 'O' was inserted into pSinCMVVac under subgenomic promoter. 5 0 UTR (untranslated region) of FMDV was introduced upstream of P1-2A to enhance the level of expression of cloned gene. Functionality of the vaccine construct was confirmed in vitro and in vivo. The self-replicating gene vaccine construct was tested in cattle in comparison with naked DNA vaccine carrying P1-2A and 3CD (pUP3CD). Humoral immune response by ELISA and SNT and cellular response by lymphoproliferation assay using MTT were studied. The default approach of using self replicating gene vaccine in high dose and multiple injection in cattle as followed in our studies might result in immunosuppression as this was observed in our subsequent experiments in guinea pigs. Hence based on dose response studies, vaccine strategy needs to be decided. However, the approach of using Sindbis polymerase gene and UTR in FMDV vaccine is the first report and shows future scope of developing such vaccines.

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“…Superior results have been consistently observed when DCs were either fused with tumor cells or when DCs were transformed by DNA or RNA compared to externally loaded DC (Refs., 13 -16,74 -76 reviewed in Refs. 38,40,77 ). Thus, besides the aspect of TH activation, the lasting availability of peptide for T cell activation appears to be of major importance.…”

Section: Discussionmentioning

confidence: 99%

Gene delivery by attenuated Salmonella typhimurium : Comparing the efficacy of helper versus cytotoxic T cell priming in tumor vaccination

Weth

Christ

Stevanović³

et al. 2001

Cancer Gene Ther

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Using the murine B16F1 melanoma, we compared a CTL -versus helper T cell ( TH ) -directed vaccination approach. Mice were either orally vaccinated with attenuated Salmonella typhimurium ( SL ) or subcutaneously with dendritic cells ( DCs ) loaded with gp100 peptides predicted to bind to H2 -Kb / H2 -Db molecules. SL were transformed with the murine gp100 cDNA ( SL -gp100 ) or with a fusion construct of gp100 and a fragment of invariant chain cDNA ( SL -gp100 / Ii ). Transcription of these genes in vivo has been readily observed in monocytes and DC. Retardation of B16F1 growth was more efficiently achieved by vaccination with SLgp100 than with DC. Vaccination with SL -gp100 / Ii aiming at preferential presentation by MHC II molecules provided some further improvement due to a stronger expansion of TH and CTL. The importance of help was further sustained by a prolongation of the survival time when mice concomitantly received IL2. Notably, prophylactic, compared to therapeutic, vaccination had no additional impact on survival time / rate. This was due to a striking decrease in frequencies of gp100 -specific TH, CTL, and cytokine -expressing cells during tumor growth. Thus, the efficacy of vaccination was limited by tumor -induced immunosuppression. Our data demonstrate the oral route of vaccination via Salmonella as a most convenient transfer regimen and confirm the superiority of protocols aiming at preferential activation of TH. Cancer Gene Therapy ( 2001 ) 8, 599 -611

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DNA and RNA-based vaccines: principles, progress and prospects

Cited by 345 publications

References 135 publications

Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing human papilloma virus E6 and E7 antigens

Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing human papilloma virus E6 and E7 antigens

Self Replicating Gene Vaccine Carrying P1-2A Gene of FMDV Serotype O and its Effects on the Immune Responses of Cattle

Gene delivery by attenuated Salmonella typhimurium : Comparing the efficacy of helper versus cytotoxic T cell priming in tumor vaccination

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