Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system.

Immunization to the model antigen ovalbumin was investigated using a novel intracutaneous delivery system consisting of antigen-coated microneedle arrays. The influence of the following parameters on the resulting immune responses was investigated: depth of vaccine delivery, dose of vaccine delivered, density of microneedles on the array, and area of application. The immune response was found to be dose dependent, and mostly independent of depth of delivery, density of microneedles, or area of application. Our studies show that the shortest, most tolerable microneedle arrays can be used for achieving consistent and high antibody titers. Overall, the microneedle array proves to be a very versatile delivery technology, allowing easy and reproducible antigen delivery to skin for efficient vaccination without the use of a needle and syringe.

[1]  J. Grivel,et al.  Immunization through dermal delivery of protein‐encoding DNA: a role for migratory dendritic cells , 1999, European journal of immunology.

[2]  R. Yu,et al.  Morphological and quantitative analyses of normal epidermal Langerhans cells using confocal scanning laser microscopy , 1994, The British journal of dermatology.

[3]  J. Hadgraft,et al.  Modified-Release Drug Delivery Technology , 2002 .

[4]  C. Alving,et al.  Transcutaneous immunization: A human vaccine delivery strategy using a patch , 2000, Nature Medicine.

[5]  M. Ameri,et al.  Optimization of an Alum-Adsorbed Vaccine Powder Formulation for Epidermal Powder Immunization , 2003, Pharmaceutical Research.

[6]  W. Vogel,et al.  Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[7]  Sueki Hairless guinea pig skin: anatomical basis for studies of cutaneous biology , 2000, European journal of dermatology : EJD.

[8]  C. Alving,et al.  Transcutaneous immunization with cholera toxin protects mice against lethal mucosal toxin challenge. , 1998, Journal of immunology.

[9]  R Panchagnula,et al.  Animal models for transdermal drug delivery. , 1997, Methods and findings in experimental and clinical pharmacology.

[10]  S. Lidén,et al.  The skin, a first level lymphoid organ? , 1970, International archives of allergy and applied immunology.

[11]  J. Matriano,et al.  Macroflux® Microprojection Array Patch Technology: A New and Efficient Approach for Intracutaneous Immunization , 2004, Pharmaceutical Research.

[12]  R. Germain,et al.  Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8+ T Cells after Gene Gun Immunization , 1998, The Journal of experimental medicine.

[13]  M. Goldfield,et al.  A comparison of the intradermal and subcutaneous routes of influenza vaccination with A/New Jersey/76 (swine flu) and A/Victoria/75: report of a study and review of the literature. , 1979, American journal of public health.

[14]  S. Muller,et al.  Immunity under the skin: potential application for topical delivery of vaccines. , 2003, Vaccine.

[15]  T. Horio,et al.  A New Animal Model for Contact Dermatitis: The Hairless Guinea Pig , 1992, The Journal of dermatology.

[16]  M. Wolf,et al.  Safety and Immunogenicity of a Prototype Enterotoxigenic Escherichia coli Vaccine Administered Transcutaneously , 2002, Infection and Immunity.

[17]  T. Louie,et al.  Comparison of Higher-Dose Intradermal Hepatitis B Vaccination to Standard Intramuscular Vaccination of Healthcare Workers , 2000, Infection Control & Hospital Epidemiology.

[18]  C. Sabella,et al.  Investigation of the pathogenesis of varicella-zoster virus infection in guinea pigs by using polymerase chain reaction. , 1993, The Journal of infectious diseases.

[19]  Y. Maa,et al.  Needle-free epidermal powder immunization , 2002, Expert review of vaccines.

[20]  S. Das,et al.  A dose-related curve of wound tensile strength following ultraviolet irradiation in the hairless guinea pig. , 1991, The American journal of the medical sciences.

[21]  M. Cormier,et al.  Macroflux Technology for Transdermal Delivery of Therapeutic Proteins and Vaccines , 2002 .

[22]  Mahmoud Ameri,et al.  Transdermal delivery of desmopressin using a coated microneedle array patch system. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[23]  G. Matyas,et al.  Transcutaneous Immunization with Bacterial ADP-Ribosylating Exotoxins as Antigens and Adjuvants , 1999, Infection and Immunity.

[24]  D. Waag,et al.  A refined guinea pig model for evaluating delayed-type hypersensitivity reactions caused by Q fever vaccines. , 1994, Laboratory animal science.

[25]  J. Bos Skin Immune System : Cutaneous Immunology and Clinical Immunodermatology, Third Edition , 2004 .

[26]  Howard I. Maibach,et al.  Models in dermatology , 1987 .

[27]  J. Serup,et al.  Topical D‐vitamins: multiparametric comparison of the irritant potential of calcipotriol, tacalcitol and calcitriol in a hairless guinea pig model , 1997, Contact dermatitis.

[28]  J. Bos Skin immune system (SIS) , 2000 .