Epidermal powder immunization: cellular and molecular mechanisms for enhancing vaccine immunogenicity.
Epidermal powder immunization (EPI) of mice with an influenza vaccine elicited consistently a higher hemagglutination inhibition (HI) antibody titers than intramuscular (IM) injection using the same dose of vaccine. The epidermal Langerhans cells (LCs) at the site of EPI were found to play an important role in the immune responses. Indeed, depletion of LCs from the immunization site prior to EPI caused a significant reduction in the antibody response. Transfer of LCs isolated from the EPI sites to naive mice induced a robust antigen-specific antibody response. Cytokines produced by target site cells appear to be important for the augmented immune responses induced by EPI. LTR72, a genetically detoxified heat-labile toxin from Escherichia coli with a strong adjuvant effect in EPI, was found to bind the keratinocytes of the epidermis, but not the LCs, and caused the production of elevated TNF-alpha and IL-12 cytokines in emigrating epidermal cells. These results have important implications for the development of a more efficacious human influenza vaccine.
Chen
Dexiang
D
PowderJect Vaccines Inc., 585 Science Drive, Madison, WI 53711, USA. dexiang_chen@powderject.com
Burger
Melissa
M
Chu
Qili
Q
Endres
Ryan
R
Zuleger
Cindy
C
Dean
Hansi
H
Payne
Lendon G
LG
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D005260:Female; D006385:Hemagglutination Inhibition Tests; D007114:Immunization / Q000379:methods; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007273:Injections, Intramuscular; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011208:Powders / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D011208:Powders