Induction of Specific Th1 Responses and Suppression of IgE Antibody Formation by Vaccination with Plasmid DNA Encoding Cyn d 1

Abstract

Background: DNA vaccines encoding allergens have been developed to prevent or to treat specific IgE responses. Objective: To evaluate the potential preventive and therapeutic effect of DNA vaccines encoding Cyn d 1 alone or combined with different adjuvants on specific allergies. Methods: Recombinant plasmid Cyn d 1 (pCyn d 1) was constructed by insertion of Cyn d 1 cDNA into the vector pcDNA3. BALB/c mice were injected with pCyn d 1 alone or plus adjuvants such as bupivacaine, bestatin, liposome, or CpG. Control mice were treated with pcDNA3 or PBS. They were boosted 3 weeks later and then sensitized twice with recombinant Cyn d 1 and alum. Their serum antibody responses and cytokine profiles of spleen cells were studied. Adoptive transfer of spleen cells of pCyn d 1-vaccinated mice was also performed. Results: Vaccination of mice with pCyn d 1 induced Th1 responses characterized by IgG2a responses and spleen cell secretion of interferon-γ. Vaccination with pCyn d 1 not only prevented the induction of specific IgE responses but also suppressed ongoing IgE responses. The mice receiving untreated, CD4+- or CD8+-depleted spleen cells from pCyn d 1-vaccinated mice all had suppression of IgE responses. Conclusion: This study confirms the prophylactic and therapeutic effects of DNA vaccines encoding Bermuda grass pollen allergen Cyn d 1 on specific IgE responses. Both CD4+ and CD8+ T cells are crucial for the immunomodulatory effect of pCyn d 1 on specific IgE responses.

Neonatal Vaccination with Plasmid DNA Encoding Cyn d 1 Effectively Prevents Allergic Responses in Mice

“…11–13 We also found that the prophylactic effect of vaccination on allergic reaction in neonatal mice is similar to that in adult animal models. 12…”

“…9,10 DNA vaccines have been shown to activate Th1 responses. 11–15 In contrast to protein vaccines, DNA vaccines induce long-lasting intracellular expression of recombinant allergens and generate specific Th1 cells that secrete predominantly interferon (IFN) γ. 13–16 IFN-γ selectively inhibits the activation of Th2 cells and B cells, which in turn results in reduced IgE production.…”

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

“…Allergens that are chemically coupled to virus-like particles [65,66] Genetic vaccines DNA vaccines -Vaccination with allergen-encoding DNA [88][89][90][91][92][93] RNA vaccines -Vaccination with allergen-encoding RNA [94] B. Alternative routes Sublingual -Sublingual administration of allergen-containing drops or tablets [17,24,[74][75][76][77][78][79] Oral -Oral administration of allergens (i.e.…”

“…Two studies performed in murine allergy models were the first to indicate that vaccination with allergen‐encoding DNA may represent a new approach for SIT [88, 89]. It has been demonstrated that genetic immunization induces allergen‐specific Th1 immune responses that may prevent allergic sensitization and eventually ongoing allergic immune responses [90, 91]. The advantage of using allergen‐encoding DNA instead of allergen for vaccination is, however, outweighed by the concern that genetic immunization may induce an uncontrolled production of allergens in treated subjects and thus may cause side effects [92].…”

Safety of engineered allergen-specific immunotherapy vaccines

“…Vaccination with plasmid DNA encoding the major Bermuda grass pollen allergen Cyn d 1 was used in combination with different adjuvants such as bupivacaine, bestatin, liposome or CpG and induced Th1 responses associated with IgG2a responses in mice. This vaccine prevented the induction of IgE responses and also suppressed ongoing IgE production in a murine model [49].…”