What is the antiallergic potential of DNA vaccination?

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Date: July 2015
From: Immunotherapy(Vol. 7, Issue 6)
Publisher: Future Medicine Ltd.
Document Type: Editorial
Length: 2,242 words
Lexile Measure: 1950L

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Author(s): Richard Weiss aff1 , Sandra Scheiblhofer aff1 , Josef Thalhamer [*] aff1


DNA vaccine; prophylaxis; RNA vaccine; skin vaccination; specific immunotherapy; type I allergy

Gene vaccines comprise a unique class of nonviral vector vaccines that have been in the focus of research for more than two decades now. Since then, elucidation of the cellular signaling pathways involved in DNA vaccine-induced immune responses [1 ] and the employment of state of the art technologies such as the use of epigenetics and 'omics' approaches has taken DNA vaccines to the edge of clinical breakthrough [2 ]. Due to their capacity to drive TH1 biased immunity, including the induction of IFN-[gamma] secreting CD4 and CD8 T cells, genetic vaccines have been predominantly investigated for antiviral immunization and in the field of cancer vaccines. However, the same features make them promising candidates for prevention and therapy of type I allergies, which are TH2-driven diseases characterized by high secretion of cytokines such as IL-4, IL-5 and IL-13, and the production of allergen-specific IgE. Many studies in mouse models have shown that the prophylactic efficacy of gene vaccines is correlated with the induction of IFN-[gamma] secreting T cells and the production of IgG2a [ 3 ]. Indeed, the authors could show that protection from sensitization is abrogated in IFN-[gamma] (but not IL-12p40) knockout mice, highlighting the importance of this cytokine concerning prophylactic efficacy [4 ]. On the other hand, the authors have also demonstrated the induction of regulatory T cells after genetic immunization [5,6 ] and found that when targeting allergens to different subcellular compartments, the absolute levels of IFN-[gamma] not necessarily correlate with protection [6 ]. These data indicate that although IFN-[gamma] seems to be a crucial component in prophylactic vaccination against allergies, other regulatory mechanisms may contribute to protective efficacy.

Antiallergic gene vaccines have also been employed in therapeutic models and have been shown to counterbalance an ongoing TH2 response, via induction of IFN-[gamma], IgG2a and suppression of IgG1, IgE and allergic lung inflammation. However, compared with prophylactic approaches, therapeutic intervention required repeated administration of the vaccines and showed only modest downregulation of the allergic phenotype. The authors therefore think that in the long run, prophylactic vaccination against allergies will be the most promising strategy as it will only require low amounts of vaccine and may provide life-long protection without requiring booster immunizations due to natural exposure to the allergen [7 ].

However, before prophylactic vaccination in humans can be considered, the safety and efficacy of gene vaccines against allergic diseases will have to be proven in therapeutic trials. Recently, in a Phase I study, the safety of a DNA vaccine encoding Cry j 2 from Japanese red cedar inserted into the Lysosomal Associated Membrane nucleic acid sequence (JRC-LAMP-Vax) was tested in healthy and sensitized subjects, all receiving four doses at 14-day intervals via intramuscular injection. Targeting the allergen to the endolysosomal compartment leads to its degradation into peptides, which are subsequently loaded on MHC-II. This approach combines two important features: it renders the vaccine 'hypoallergenic',...

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Gale Document Number: GALE|A422428329