Adjuvantation of epidermal powder immunization.
The skin is an immunologically active site and an attractive vaccination route. All current vaccines, however, are administered either orally, intramuscularly, or subcutaneously. We previously reported that epidermal powder immunization (EPI) with an extremely small dose of powdered influenza vaccine induces protective immunity in mice. In this study, we report that commonly used adjuvants can be used in EPI to further enhance the immune responses to an antigen. The IgG antibody response to diphtheria toxoid (DT) following EPI was augmented by 25- and 250-fold, when 1 microg DT was co-delivered with aluminum phosphate (alum) and a synthetic oligonucleotide containing CpG DNA motifs (CpG DNA), respectively. These antibodies had toxin-neutralization activity and were long lasting. Furthermore, EPI using an adjuvant selectively activated different subsets of T helper cells and gave either a Th1 or a Th2 type of immune response. Similar to needle injection into deeper tissues, EPI with alum adsorbed DT promoted a predominantly IgG1 subclass antibody response and elevated level of IL-4 secreting cells. These are indicative of Th2-type immunity. In contrast, co-delivery of CpG DNA adjuvant via EPI led to Th-1 type of response as characterized by the increased production of IgG2a antibodies and IFN-gamma secreting cells. This study indicated that EPI using appropriate adjuvants can produce an augmented antibody response and desirable cellular immune responses. EPI is a promising immunization method that may be used to administer a broad range of vaccines including vaccines with adjuvants.
PowderJect Vaccines Inc., 585 Science Drive, Madison, WI 53711, USA. dexiang_chen@powderject.com
D
D
Chen
C A
CA
Erickson
R L
RL
Endres
S B
SB
Periwal
Q
Q
Chu
C
C
Shu
Y F
YF
Maa
L G
LG
Payne
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000096:biosynthesis; D015226:Dinucleoside Phosphates / Q000008:administration & dosage; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011208:Powders; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage*; D014709:Vero Cells
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D016207:Cytokines; D015226:Dinucleoside Phosphates; D004168:Diphtheria Toxoid; D007074:Immunoglobulin G; D011208:Powders; D014612:Vaccines; C015772:CpG dinucleotide