Cationic transfersomes based topical genetic vaccine against hepatitis B.
DNA vaccines have been shown to elicit both cellular and humoral immune responses and to be effective in a variety of preclinical bacterial, viral, and parasitic animal models. We have recently described a needle-free method of vaccination, transcutaneous immunization, based on topical application of vaccine antigens on intact skin using a novel carrier system, namely transfersomes. In the present study, a novel modified version of transfersomes, i.e., cationic transfersomes for topical DNA vaccine delivery has been developed. Cationic transfersomes composed of cationic lipid DOTMA and sodium deoxycholate as constitutive lipids were prepared and optimized for their size, shape, zeta potentials, deformability and loading efficiency. Plasmid DNA encoding hepatitis B surface antigen (HBsAg) was loaded in the cationic transfersomes using charge neutralization method. The immune stimulating activity was studied by measuring serum anti-HBsAg titer and cytokines level (IL-2 and IFN-gamma) following topical applications of plasmid DNA loaded cationic transfersomes in Balb/c mice and results were compared with naked DNA applied topically as well as naked DNA and pure recombinant HBsAg administered intramuscularly. Results revealed that DNA loaded cationic transfersomes elicited significantly (*P<0.05) higher anti-HBsAg antibody titer and cytokines level as compared to naked DNA. It was also observed that topical application of DNA loaded cationic transfersomes elicited a comparable serum antibody titer and endogenous cytokines levels as produced after intramuscular recombinant HBsAg administration. The study signifies the potential of cationic transfersomes as DNA vaccine carriers for effective topical immunization.
Mahor
Sunil
S
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, MP 470003, India.
Rawat
Amit
A
Dubey
Praveen K
PK
Gupta
Prem N
PN
Khatri
Kapil
K
Goyal
Amit K
AK
Vyas
S P
SP
D000818:Animals; D000917:Antibody Formation; D002412:Cations; D003840:Deoxycholic Acid / Q000737:chemistry*; D005260:Female; D018014:Gene Transfer Techniques; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013997:Time Factors; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D002412:Cations; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007376:Interleukin-2; D000644:Quaternary Ammonium Compounds; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D003840:Deoxycholic Acid; C054005:N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium; D007371:Interferon-gamma