Induction of a Th1 immune response and suppression of IgE via immunotherapy with a recombinant hybrid molecule encapsulated in liposome-protamine-DNA nanoparticles in a model of experimental allergy.

Abstract

Liposome-protamine-DNA nanoparticles (LPD) are safe, effective, and non-toxic adjuvants that induce Th1-like immune responses. We hypothesized that encapsulation of allergens into liposomes could be an appropriate option for immunotherapy. The present study evaluated the immunotherapeutic potential of a recombinant hybrid molecule (rHM) encapsulated in LPD nanoparticles in a murine model of Chenopodium album allergy. BALB/c mice were sensitized with the allergen in alum, and the immunotherapy procedure was performed by subcutaneous injections of LPD-rHM, rHM, or empty LPD at weekly intervals. Sensitized mice developed a Th2-biased immune response characterized by strong specific IgG1 and IgE production, IL-4, and the transcription factor GATA3 in spleen cell cultures. Treatment with the LPD-rHM resulted in a reduction in IgE and a marked increase in IgG2a. The LPD-rHM induced allergen-specific responses with relatively high interferon-gamma production, as well as expression of the transcription factor T-bet in stimulated splenocytes. In addition, lymphoproliferative responses were higher in the LPD-rHM-treated mice than in the other groups. Removal of the nanoparticles from the rHM resulted in a decrease in the allergen's immunogenicity. These results indicate that the rHM complexed with LPD nanoparticles has a marked suppressive effect on the allergic response and caused a shift toward a Th1 pathway.

• Authors: Hamid Reza Nouri, Abdolreza Varasteh, Mahmoud Reza Jaafari, Janet M Davies, Mojtaba Sankian
• Journal: Immunologic research (Immunol Res) Vol. 62 Issue 3 Pg. 280-91 (Jul 2015) ISSN: 1559-0755 [Electronic] United States
• PMID: 25957889 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GATA3 Transcription Factor
• Gata3 protein, mouse
• Immunoglobulin G
• Liposomes
• Nanocapsules
• Protamines
• Recombinant Proteins
• T-Box Domain Proteins
• T-box transcription factor TBX21
• Interleukin-4
• Immunoglobulin E
• Interferon-gamma
• DNA

Topics

• Animals
• Chenopodium album (immunology)
• DNA (pharmacology)
• Female
• GATA3 Transcription Factor (metabolism)
• Hypersensitivity (drug therapy, immunology)
• Immunoglobulin E (biosynthesis, immunology)
• Immunoglobulin G (immunology)
• Immunotherapy
• Interferon-gamma (biosynthesis)
• Interleukin-4 (metabolism)
• Liposomes (pharmacology)
• Mice
• Mice, Inbred BALB C
• Nanocapsules
• Protamines (pharmacology)
• Random Allocation
• Recombinant Proteins
• T-Box Domain Proteins (biosynthesis)
• Th1 Cells (immunology)
• Th2 Cells (immunology)