Intranasal immunization with DNA vaccine coexpressing Der p 1 and ubiquitin in an allergic rhinitis mouse model

Ann Allergy Asthma Immunol. 2014 Dec;113(6):658-665.e1. doi: 10.1016/j.anai.2014.08.015. Epub 2014 Sep 17.

Abstract

Background: The worldwide prevalence of allergic rhinitis (AR) is increasing, whereas treatments for AR remain limited in effect. Therefore, a new type of effective drug is eagerly in demand.

Objective: To create a hypoallergenic vaccine by forced ubiquitination.

Methods: In the present study, we constructed a DNA vaccine coexpressing Der p 1 allergen and murine ubiquitin, which used chitosan as a carrier. Through the vitro and vivo experiments, we evaluated its protective efficacy against AR.

Results: The results indicated that the DNA vaccine pVAX1-Ub-Derp1/CS had been successfully constructed. This nanoparticle could not only transfect 293T cells in vitro but also transform cells in vivo. The inflammation of nasal mucosa in an AR murine model via immunization with pVAX1-Ub-Derp1/CS was less severe than those without treatments. Furthermore, it found that mice immunized with pVAX1-Ub-Derp1/CS generated a high level of specific IgG but a low level of specific IgE (P < .01). The significantly increased levels of interferon-γ and the significantly decreased levels of interleukins 4, 10, and 17 indicated that a TH1-type response was elicited by immunization with pVAX1-Ub-Derp1/CS (P < .01). This effect was especially stronger through intranasal immunization.

Conclusion: Nasal mucosal immunization and ubiquitination are efficacious strategies to enhance the efficiency and safety of DNA vaccine. The nanoparticle pVAX1-Ub-Derp1/CS is expected to be a new kind of effective vaccine for AR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antigens, Dermatophagoides / genetics
  • Antigens, Dermatophagoides / immunology*
  • Arthropod Proteins / genetics
  • Arthropod Proteins / immunology*
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / immunology*
  • Desensitization, Immunologic / methods
  • Disease Models, Animal
  • Gene Expression / immunology
  • HEK293 Cells
  • Humans
  • Immunization*
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-17 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage
  • Nasal Mucosa / immunology*
  • Nasal Mucosa / physiopathology
  • Plasmids / immunology
  • Rhinitis, Allergic / immunology
  • Rhinitis, Allergic / physiopathology
  • Rhinitis, Allergic / prevention & control*
  • Th1-Th2 Balance
  • Ubiquitin / genetics
  • Ubiquitin / immunology*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • IL10 protein, mouse
  • Immunoglobulin G
  • Interleukin-17
  • Ubiquitin
  • Vaccines, DNA
  • Interleukin-10
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma
  • Cysteine Endopeptidases
  • Dermatophagoides pteronyssinus antigen p 1