Nanopatch targeted delivery of both antigen and adjuvant to skin synergistically drives enhanced antibody responses.
Many vaccines make use of an adjuvant to achieve stronger immune responses. Alternatively, potent immune responses have also been generated by replacing the standard needle and syringe (which places vaccine into muscle) with devices that deliver vaccine antigen to the skin's abundant immune cell population. However it is not known if the co-delivery of antigen plus adjuvant directly to thousands of skin immune cells generates a synergistic improvement of immune responses. In this paper, we investigate this idea, by testing if Nanopatch delivery of vaccine - both the antigen and the adjuvant - enhances immunogenicity, compared to intramuscular injection. As a test-case, we selected a commercial influenza vaccine as the antigen (Fluvax 2008®) and the saponin Quil-A as the adjuvant. We found, after vaccinating mice, that anti-influenza IgG antibody and haemagglutinin inhibition assay titre response induced by the Nanopatch (with delivered dose of 6.5ng of vaccine and 1.4μg of Quil-A) were equivalent to that of the conventional intramuscular injection using needle and syringe (6000ng of vaccine injected without adjuvant). Furthermore, a similar level of antigen dose sparing (up to 900 fold) - with equivalent haemagglutinin inhibition assay titre responses - was also achieved by delivering both antigen and adjuvant (1.4μg of Quil-A) to skin (using Nanopatches) instead of muscle (intramuscular injection). Collectively, the unprecedented 900 fold antigen dose sparing demonstrates the synergistic improvement to vaccines by co-delivery of both antigen and adjuvant directly to skin immune cells. Successfully extending these findings to humans with a practical delivery device - like the Nanopatch - could have a huge impact on improving vaccines.
The University of Queensland, Delivery of Drugs and Genes Group, Australian Institute for Bioengineering and Nanotechnology, Brisbane, QLD 4072, Australia.
Germain J P
GJ
Fernando
Xianfeng
X
Chen
Clare A
CA
Primiero
Sally R
SR
Yukiko
Emily J
EJ
Fairmaid
Holly J
HJ
Corbett
Ian H
IH
Frazer
Lorena E
LE
Brown
Mark A F
MA
Kendall
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000097:blood*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures; D009975:Orthomyxoviridae / Q000276:immunology; D062605:Quillaja Saponins; D012503:Saponins / Q000008:administration & dosage* / Q000276:immunology; D012867:Skin / Q000276:immunology*; D013499:Surface Properties; D057968:Transdermal Patch
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D062605:Quillaja Saponins; D012503:Saponins; C046386:Quil A