Development of novel fusogenic vesosomes for transcutaneous immunization.
Transcutaneous immunization (TCI) is a novel vaccination strategy based on the application of antigen together with an adjuvant onto hydrated bare skin. This simple and non-invasive immunization procedure elicits systemic and cell mediated immune responses and therefore, it provides a viable and cost-effective strategy for disease prevention. In the present study, novel fusogenic vesicular carrier constructs, i.e. vesosomes were developed and evaluated for topical delivery of vaccines using tetanus toxoid (TTx) as a model antigen. Prepared vesosomes were characterized for size, shape, entrapment efficiency and zeta potential. The prepared novel systems were examined for in process antigen stability and long-term storage stability studies. In vitro skin permeation and fluorescence microscopy study were also preformed for prepared novel vesicular systems for the evaluation of skin penetration efficiency. The immune stimulating activity of these vesicles was studied by measuring the serum anti-tetanus toxoid IgG titer and isotype ratio IgG2a/IgG1 following topical immunization in three different protocols and results were compared with the alum adsorbed tetanus toxoid given intramuscularly and topically administered plain tetanus toxoid solution, plain liposomes and cationic fusogenic liposomes. Serum IgG titers after three consecutive topical administrations were significantly better (*P < 0.05) than single administration of TTx antigen with vesosomal systems, suggesting an effective stimulation of serum immune response. Furthermore, notable serum anti-TTx antibody titers also occurred in animals primed with alum adsorbed TTx and subsequently boosted with topical administration of novel vesosomal systems. In each immunization studies, the vesosomal systems could elicit combined Th1 and Th2 immune responses following topical administration. These results suggest that the investigated vesosomal systems can be effective as topical delivery of vaccines.
Mishra
Vivek
V
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, Madhya Pradesh 470003, India.
Mahor
Sunil
S
Rawat
Amit
A
Dubey
Praveen
P
Gupta
Prem N
PN
Singh
Paramjit
P
Vyas
Suresh P
SP
D000279:Administration, Cutaneous; D000818:Animals; D000941:Antigens / Q000276:immunology*; D002459:Cell Fusion / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004705:Endocytosis / Q000502:physiology; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D051381:Rats; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology; D022161:Transport Vesicles / Q000276:immunology*
D000941:Antigens; D007074:Immunoglobulin G; D008081:Liposomes; D013745:Tetanus Toxoid