Immune responses to hepatitis B surface antigen following epidermal powder immunization.
Langerhans cells in the epidermis of skin are potent antigen-presenting cells that trigger the immune system to respond to invading microorganisms. We have previously shown that epidermal powder immunization with a powdered inactivated influenza virus vaccine, by targeting the Langerhans cell-rich epidermis, was more efficacious than deeper tissue injection using a needle and syringe. We now report enhanced humoral and cellular immune responses to recombinant hepatitis B surface antigen following epidermal powder immunization. We observed that epidermal powder immunization with unadjuvanted hepatitis B surface antigen elicited an antibody titre equivalent to that induced by the alum-adjuvanted vaccine delivered by intramuscular injection, suggesting that epidermal powder immunization can overcome the need for adjuvantation. We demonstrated that synthetic CpG oligonucleotides (CpG DNA) could be coformulated with hepatitis B surface antigen and delivered by epidermal powder immunization to further augment the antibody response and modulate T helper cell activities. Epidermal powder immunization of hepatitis B surface antigen formulated with CpG DNA formulations resulted in 1.5-2.0 logs higher IgG antibody titres than alum-adjuvanted commercial vaccines administered by intramuscular injection. Formulation of hepatitis B surface antigen with CpG DNA elicited an augmented IgG2a antibody response and increased frequency of IFN-gamma secreting cells. In addition, CpG DNA was found to activate epidermal Langerhans cells and stimulate the production of TNF-alpha and IL-12 cytokines by epidermal cells, explaining its strong adjuvant activity following epidermal powder immunization. These results show that epidermal powder immunization is a safe and effective method to deliver hepatitis B surface antigen and the addition of new adjuvants, such as CpG DNA, may further enhance the efficacy of this vaccine.
Osorio
Jorge E
JE
PowderJect Vaccines Inc., Madison, Wisconsin, USA. jorge_osorio@powderject.com
Zuleger
Cindy L
CL
Burger
Melissa
M
Chu
Qili
Q
Payne
Lendon G
LG
Chen
Dexiang
D
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000276:immunology / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004817:Epidermis / Q000187:drug effects; D005260:Female; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D016207:Cytokines; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D014612:Vaccines; C041524:aluminum sulfate; D004247:DNA