Bins, A. et al. A rapid and potent DNA vaccination strategy defined by in vivo monitoring of antigen expression. Nat. Med. 11, 899-904

Johns Hopkins University, Baltimore, Maryland, United States
Nature Medicine (Impact Factor: 27.36). 09/2005; 11(8):899-904. DOI: 10.1038/nm1264
Source: PubMed


Induction of immunity after DNA vaccination is generally considered a slow process. Here we show that DNA delivery to the skin results in a highly transient pulse of antigen expression. Based on this information, we developed a new rapid and potent intradermal DNA vaccination method. By short-interval intradermal DNA delivery, robust T-cell responses, of a magnitude sufficient to reject established subcutaneous tumors, are generated within 12 d. Moreover, this vaccination strategy confers protecting humoral immunity against influenza A infection within 2 weeks after the start of vaccination. The strength and speed of this newly developed strategy will be beneficial in situations in which immunity is required in the shortest possible time.

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    • "The tattooing procedure is robust, easy to use, fully hygienic and beneficiates from decades of development by the cosmetic industry. Tattooing administration has already been used in medical research to define a DNA vaccination strategy3. However, to our knowledge the current study is the first to investigate drug-delivery via tattooing to treat a skin disease. "
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    ABSTRACT: This study establishes a proof-of-concept that a tattoo device can target intra-dermal drug delivery against cutaneous leishmaniasis (CL). The selected drug is oleylphosphocholine (OlPC) formulated as liposomes, particles known to be prone to macrophage ingestion. We first show that treatment of cultured Leishmania-infected macrophages with OlPC-liposomes results in a direct dose-dependent killing of intracellular parasites. Based on this, in vivo efficacy is demonstrated using a 10 day tattooing-mediated treatment in mice infected with L. major and L. mexicana. In both models this regimen results in rapid clinical recovery with complete regression of skin lesions by Day 28. Parasite counts and histopathology examination confirm high treatment efficacy at the parasitic level. Low amount of drug required for tattooing combined with fast clinical recovery may have a positive impact on CL patient management. This first example of tattoo-mediated drug delivery could open to new therapeutic interventions in the treatment of skin diseases.
    Full-text · Article · Feb 2014 · Scientific Reports
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    • "Vaccines have been shown to vary widely in potency based on the duration and kinetic profile of exposure to antigen and adjuvant combinations.25–30 Recently, we demonstrated that intra-lymph node injection of vaccines composed of soluble protein mixed with sustained-release adjuvant-loaded polymer particles could dramatically enhance the immune response to a model protein antigen.30 "
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    ABSTRACT: Transcutaneous administration has the potential to improve therapeutics delivery, providing an approach that is safer and more convenient than traditional alternatives, while offering the opportunity for improved therapeutic efficacy through sustained/controlled drug release. To this end, we demonstrate a microneedle materials platform for rapid implantation of controlled-release polymer depots into the cutaneous tissue. Arrays of microneedles comprised of drug-loaded poly(lactide-co-glycolide) (PLGA) microparticles or solid PLGA tips were prepared with a supporting and rapidly water-soluble poly(acrylic acid) (PAA) matrix. Upon application of microneedle patches to the skin of mice, the microneedles perforated the stratum corneum and epidermis. Penetration of the outer skin layers was followed by rapid dissolution of the PAA binder on contact with the interstitial fluid of the epidermis, implanting the microparticles or solid polymer microneedles in the tissue, which were retained following patch removal. These polymer depots remained in the skin for weeks following application and sustained the release of encapsulated cargos for systemic delivery. To show the utility of this approach we demonstrated the ability of these composite microneedle arrays to deliver a subunit vaccine formulation. In comparison to traditional needle-based vaccination, microneedle delivery gave improved cellular immunity and equivalent generation of serum antibodies, suggesting the potential of this approach for vaccine delivery. However, the flexibility of this system should allow for improved therapeutic delivery in a variety of diverse contexts.
    Full-text · Article · Jan 2013 · Advanced Functional Materials
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    • "The plasmid can be enclosed in cationic liposomes to protect it against nucleases12 or shot into the dermis after coating it on gold particles by exploiting a “gene gun”13 or jet-injectors.14 Lastly, a rapid immune response follows tattooing of a plasmid into the skin.15 "
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    ABSTRACT: The emerging evidence that DNA vaccines elicit a protective immune response in rodents, dogs and cancer patients, coupled with the US Food and Drug Administration (FDA) approval of an initial DNA vaccine to treat canine tumors is beginning to close the gap between the optimistic experimental data and their difficult application in a clinical setting. Here we review a series of conceptual and biotechnological advances that are working together to make DNA vaccines targeting molecules that play important roles during cancer progression (oncoantigens) a promise with near-term clinical impact.
    Full-text · Article · May 2012 · OncoImmunology
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