The Adjuvantal Effect Of Imiquimod On Transcutaneous Immunization

Human's skin has a large surface area. It is the largest tissue and organ of person.Skin has been regarded as a organ that has peculiar immune function and keeps closecorrelation with immunity system.Langerhans cells are paradigmatic dendriticcells, described in 1868 by a youngmedical student, Paul Langerhans in Berlin. Langerhans cells are present withepithelial cells in the epidermis, bronchi and mucosae. After antigenic challenge,Langerhans cells migrate into the T cell areas of proximal lymph nodes where they actas professional antigen-presenting cells.Transcutaneous immunization (TCI) is a novel strategy for administering adjuvantand antigen to the skin surface. The adjuvant and antigen applied using TCIapparently target Langerhans cells in the skin, eliciting systemic antibodies, includingrobust mucosal IgG and secretory IgA responses in both mice and humans andprotective immunity against mucosal challenge with toxin or live virus.Karande describe particular mixtures of penetration enhancers that increase skinpermeability to macromolecules (＜1-10 kDa) by up to＜100-fold without inducingskin irritation. In vitro experiments demonstrated that the mixtures deliveredmacromolecular drugs, including heparin, leutinizing hormone releasing hormone(LHRH) and oligonulceotides across the skin. In vivo experiments on hairless ratswith leuprolide acetate confirmed the potency and safety of one such mixture, sodiumlaureth sulfate (SLA) and phenylpiperazine (PP).Imiquimod, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (also knownas R-837 and S-26308), is a nonnucleoside heterocyclic amine that belongs to a classof products known as immune-response modifiers. In vivo studies have demonstratedthat imiquimod is a potent inducer of alpha IFN(IFN-a), tumor necrosis factor alpha(TNF-a), and interleukin-1,6,8,10,12 (IL-1,6,8,10,12) and that it has adjuvantproperties greater than those of Freund's complete adjuvant. In animal models,imiquimod has been demonstrated to have potent antiviral and antitumor effects.We use the imiquimod as adjuvant to investigate the adjuvantal effect of imiquimod on transcutaneous immunization for subunit antigen, virus antigen and DNA vaccine.SLA: PP (weight fractions,0.7:0.3;total concentration of 0.5%(wt/vol)) dissolves in1:1 phosphate buffered saline(PBS):ethanol. This solution admixes with HBV subunitantigen, HAV antigen and HBsAg DNA vaccine distinctively. The admixtures werebesmeared on the depilated mouse back and then the adjuvant imiquimod wasbesmeared on the back. At 2, 4, 6, 8, 12, 20 weeks post inoculation. The specificHBsAg antibody were detected early at two weeks after transcutaneous immunization.The titers reached the highest level at 8 weeks. The array without imiquimod coulddetect antibody only at 4 weeks post immunization.Conclusion The adjuvant imiquimod can enhance specific antibody levelsignificantly and quickly for HBsAg and HBsAg DNA vaccine.