Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines

@article{Carralot2004PolarizationOI,
  title={Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines},
  author={Jean-Philippe Carralot and Jochen Probst and Ingmar Hoerr and Birgit Scheel and Regina Teufel and Günther Jung and Hans-Georg Rammensee and Steve Pascolo},
  journal={Cellular and Molecular Life Sciences},
  year={2004},
  volume={61},
  pages={2418 - 2424}
}
AbstractIn 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… 
Vaccination with messenger RNA.
  • S. Pascolo
  • Biology
    Methods in molecular medicine
  • 2006
TLDR
This chapter describes the production of mRNA and the preparation of the two types of mRNA-based vaccines tested in humans, which are being evaluated in human clinical trials.
Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis
TLDR
Vaccination of mice with a single dose of naked mRNA-Hsp65 through intranasal route was able to induce protection against subsequent challenge with virulent strain of Mycobacterium tuberculosis, showing a novel and efficient strategy to control experimental tuberculosis.
Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ
TLDR
The utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein is explored.
mRNA Vaccination and Personalized Cancer Therapy
TLDR
This chapter provides a short summary of the history of mRNA-based vaccination and introduces into the design and production of mRNA vaccines, and provides insights into the preclinical development and clinical translation of personalized mRNA vaccines which are tailored to the antigen profile of individual cancer patients.
Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity.
TLDR
In tumor-bearing mice intralymphatic RNA vaccination elicited protective and therapeutic antitumor immune responses, resulting in a remarkable survival benefit as compared with other treatment regimens.
A novel, disruptive vaccination technology
TLDR
Initial clinical experiences suggest that the preclinical immunogenicity of RNActive® could be successfully translated to humans and protect against lethal challenges with a variety of different influenza strains in preclinical models.
Direct Injection of Protamine-protected mRNA: Results of a Phase 1/2 Vaccination Trial in Metastatic Melanoma Patients
TLDR
It is shown here that direct injection of protamine-protected mRNA is feasible and safe and the significant influence of the treatment on the frequency of immunosuppressive cells, the increase of vaccine-directed T cells upon treatment in a subset of patients together with the demonstration of a complete clinical response encourage further clinical investigation of the protamines-mRNA vaccine.
Uptake of synthetic naked RNA by skin-resident dendritic cells via macropinocytosis allows antigen expression and induction of T-cell responses in mice
TLDR
It is demonstrated that direct antigen translation by dermal DCs after intradermal naked RNA vaccination is relevant for efficient priming of antigen-specific T-cells.
Results of the First Phase I/II Clinical Vaccination Trial With Direct Injection of mRNA
TLDR
It is demonstrated here that such treatment is feasible and safe (phase 1 criteria) and an increase in antitumor humoral immune response was seen in some patients, however, a demonstration of clinical effectiveness of direct injection of copy mRNA for antitumors immunotherapy was not shown in this study and must be evaluated in subsequent trials.
mRNA Modification and delivery strategies towards the establishment of a platform for safe and effective gene therapy
TLDR
The presented data demonstrate that the recognition of mRNA by the innate immune system is also associated with cell death, which proceeds in human respiratory cells via pyroptosis, a form of programmed cell death mediated by overexpression of caspase-1.
...
...

References

SHOWING 1-10 OF 29 REFERENCES
Enhanced CTL responses mediated by plasmid DNA immunogens encoding costimulatory molecules and cytokines.
TLDR
The coexpression of certain costimulatory molecules and/or cytokines, in concert with a non-self gene delivered as an intramuscular plasmid DNA immunogen, can significantly enhance Ag-specific CTL responses.
Cytokine-facilitated priming of CD8+ T cell responses by DNA vaccination
TLDR
The codelivery of GM-CSF encoding plasmid DNA primed potent, specific CTL immunity detected either in a cytotoxic assay or by determining the frequency of Ld-restricted CD8+ T cells specifically inducible to IFNγ production.
Cancer therapy using a self-replicating RNA vaccine
TLDR
The enhanced efficacy in vivo correlated with a caspase-dependent apoptotic death in transfected cells, providing a potential mechanism for enhanced immunogenicity.
Intra-pinna anti-tumor vaccination with self-replicating infectious RNA or with DNA encoding a model tumor antigen and a cytokine
TLDR
Efficient protective antitumor immunity after intra-pinna lacZ TAA polynucleotide vaccination is demonstrated and additional immunomodulatory effects by co-administration of cytokine polyn nucleotides are shown.
Gene inoculation generates immune responses against human immunodeficiency virus type 1.
  • B. WangK. Ugen D. Weiner
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993
TLDR
The gene inoculation technique mimics features of vaccination with live attenuated viruses and, therefore, may ultimately prove useful in the rapid development of safe and efficacious vaccines as it provides for production of relevant antigen in vivo without the use of infectious agents.
DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations.
TLDR
By far the most efficient DNA immunizations were achieved by using a gene gun to deliver DNA-coated gold beads to the epidermis, and 95% protection was achieved by two immunizations with beads loaded with as little as 0.4 micrograms of DNA.
In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies
TLDR
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.
Technical and regulatory hurdles for DNA vaccines.
Induction of virus‐specific cytotoxic T lymphocytes in vivo by liposome‐entrapped mRNA
TLDR
The induction of anti‐influenza cytotoxic T lymphocytes (CTL) in vivo by immunizing mice with liposomes containing messenger RNA (mRNA) encoding the influenza virus nucleoprotein (NP) is described and the relevance of these results in the context of vaccine development is discussed.
RNA as a tumor vaccine: a review of the literature
TLDR
The possible utility of RNA‐based vaccines for tumor immunotherapy should be further explored to determine whether such approaches are clinically useful.
...
...