Neonatal vaccination with plasmid DNA encoding Cyn d 1 effectively prevents allergic responses in mice.

BACKGROUND: Allergic rhinitis is one of the most common atopic disorders in children. There is no available method to prevent airway sensitization in newborns except allergen avoidance. Recombinant DNA plasmids encoding allergens have been proven to activate Th1 but attenuate Th2-deviated allergic responses in adult animal studies. However, their preventive effects are not presumptive in neonates because of their immature immune function. The aim of this study was to examine the potential preventive effect of a DNA vaccine encoding grass pollen allergen Cyn d 1 on allergic reaction to grass pollen in neonatal mice. METHODS: Recombinant plasmid Cyn d 1 (pCyn d 1) vaccine was constructed by insertion of Cyn d 1 cDNA into the vector pcDNA3. Neonatal BALB/c mice received the vaccine once on the 3rd day of life or a second dose 2 days later. Control mice received PBS only. Mice were sensitized twice with recombinant Cyn d 1 and alum beginning at 7 weeks of age. Serum antibody responses and cytokine profiles of spleen cells were examined. RESULTS: Neonatal injection with pCyn d 1 vaccine resulted in IgG2a responses and production of interferon gamma in spleen cells. Vaccination with pCyn d 1 also reduced specific IgE responses and spleen cell secretion of IL-4. CONCLUSION: This study shows the prophylactic effects of DNA vaccine encoding Bermuda grass pollen allergen Cyn d 1 on specific IgE responses in neonatal mice.

Induction of specific Th1 responses and suppression of IgE antibody formation by vaccination with plasmid DNA encoding Cyn d 1.

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.