Cationic liposomes as potential carriers for ocular administration of peptides with anti-herpetic activity.
In the present study the preparation, characterization and activity of cationic liposomes containing the secretory form of herpes simplex virus type 1 (HSV-1) glycoprotein B (gB1s) or two related polylysine rich peptides, namely DTK1 and DTK2, were described. The immunotherapeutic potential of these HSV antigens containing liposomes was examined with a rabbit ocular model of HSV-1 infection. Our study indicates that the liposomes (i) are able to encapsulate quantitatively gB1s and around 30% the DTK peptides, (ii) are characterized by dimensions compatible with ocular applications and (iii) can release the peptide comparably to the free solution. In addition, neutralization studies demonstrated that an anti-DTK specific polyclonal antiserum can inhibit HSV-1 infection, indicating that such peptides could be a good immunogen/antigen in an anti-HSV vaccine formulation. Although the vaccination protocol did not induce protection against the eye disease, a significative protection against a lethal ocular challenge was detectable together with the absence of reactivation episodes from latency on the survived animals. In this respect, the use of cationic liposomes coupled to gB1s and DTK peptides, as a local ocular vaccine, could represent an interesting approach in order to obtain a possible efficacy in protecting animals against a subsequent HSV-1 ocular challenge.
Cortesi
R
R
Department of Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
Argnani
R
R
Esposito
E
E
Dalpiaz
A
A
Scatturin
A
A
Bortolotti
F
F
Lufino
M
M
Guerrini
R
R
Cavicchioni
G
G
Incorvaia
C
C
Menegatti
E
E
Manservigi
R
R
D000818:Animals; D002522:Chlorocebus aethiops; D016503:Drug Delivery Systems; D005123:Eye / Q000821:virology; D005260:Female; D006561:Herpes Simplex / Q000517:prevention & control* / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage*; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000472:pathogenicity; D008081:Liposomes; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis; D011817:Rabbits; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000008:administration & dosage*
C515401:DTK1 peptide; C515402:DTK2 peptide; D022301:Herpes Simplex Virus Vaccines; D008081:Liposomes; D010455:Peptides; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus