Nano-sized Soluplus® polymeric micelles enhance the induction of tetanus toxin neutralising antibody response following transcutaneous immunisation with tetanus toxoid.
The use of Soluplus® polymeric micelles as a novel adjuvant for tetanus toxoid (TTxd) in transcutaneous immunisation was evaluated. TTxd was added to Soluplus® polymeric micelles to form TTxd-Soluplus® nano-aggregates with a size of 68nm. Non-adjuvanted TTxd commonly induces very poor antibody response by the transcutaneous route. However, in this study, the use of TTxd-Soluplus® resulted in a significant increase in the antibody response to TTxd, which was similar to that induced in the presence of CPG-oligodeoxynucleotides (CPG-ODNs) adjuvant. The toxin neutralising potency of the immune sera induced by TTxd-Soluplus® was also much stronger than that from TTxd alone, in a passive transfer experiment in mice. Soluplus® also enhanced the immunogenicity of the toxoid when TTxd-Soluplus® was stored at 4°C for 4weeks, but not at higher temperatures. Confocal microscopy imaging showed a much higher uptake of TTxd in the epidermis and dermis layers of the skin when it was associated with Soluplus®, suggesting that the mechanism for Soluplus® adjuvanticity is through enhanced uptake of the TTxd through the skin. Overall, our findings demonstrated that Soluplus® is an effective novel adjuvant for transcutaneous immunisation.
Bacteriology Division, National Institute for Biological Standards and Control (NIBSC), MHRA, Potters Bar, Hertfordshire EN6 3QG, UK.
Manolya
M
Saydam
Department of Pharmacy, Pharmacology and Postgraduate Medicine, School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK.
Woei Ping
WP
Cheng
Bacteriology Division, National Institute for Biological Standards and Control (NIBSC), MHRA, Potters Bar, Hertfordshire EN6 3QG, UK.
Nathan
N
Palmer
Bacteriology Division, National Institute for Biological Standards and Control (NIBSC), MHRA, Potters Bar, Hertfordshire EN6 3QG, UK.
Robert
R
Tierney
Biological Imaging Group, Analytical Sciences Division, NIBSC, UK.
Robert
R
Francis
Biological Imaging Group, Analytical Sciences Division, NIBSC, UK.
Kirsty
K
MacLellan-Gibson
Department of Pharmacy, Pharmacology and Postgraduate Medicine, School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK.
Ambreen
A
Khan
Bacteriology Division, National Institute for Biological Standards and Control (NIBSC), MHRA, Potters Bar, Hertfordshire EN6 3QG, UK. Electronic address: fmawas@nibsc.ac.uk.
Fatme
F
Mawas
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000917:Antibody Formation; D000992:Antitoxins / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D007116:Immunization, Passive; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011145:Polyvinyls / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D013742:Tetanus / Q000517:prevention & control; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000992:Antitoxins; D011145:Polyvinyls; D013745:Tetanus Toxoid; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols
Nanotechnology; Neutralising antibodies; Polymeric micelles; Tetanus toxoid; Transcutaneous delivery