Mucosal immunization against hepatitis A: antibody responses are enhanced by co-administration of synthetic oligodeoxynucleotides and a novel cationic lipid.
Hepatitis A caused by hepatitis A virus (HAV) transmitted by the fecal-oral route, results in considerable morbidity and economic loss. Mucosal immunization can be more effective than conventional injection at inducing both local and systemic immunity to HAV. Here we show that co-administration of killed HAV with synthetic oligodeoxynucleotides (ODNs) containing CpG sequences, and a novel polycationic sphingolipid (CCS)/cholesterol liposomal delivery system, markedly enhances the HAV-specific antibody response at the intestinal interface, particularly when delivered intrarectally or intranasally, to Balb/c mice at low HAV doses. A mucosally delivered, antigen-sparing HAV vaccine that is easily administered without specialized equipment or personnel, is an attractive alternative for facilitating mass immunization in hepatitis A outbreaks.
Mitchell
Leslie Ann
LA
Goldyne Savad Gene Therapy Institute, Hadassah Medical Organization, Kiryat Ein Karem, Jerusalem 91120, Israel. Leah_Bellehsen@yahoo.ca
Joseph
Aviva
A
Kedar
Eli
E
Barenholz
Yechezkel
Y
Galun
Eitan
E
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D002412:Cations; D002784:Cholesterol / Q000008:administration & dosage; D005260:Female; D006506:Hepatitis A / Q000276:immunology / Q000517:prevention & control*; D035922:Hepatitis A Antibodies / Q000097:blood*; D022362:Hepatitis A Vaccines / Q000008:administration & dosage* / Q000276:immunology; D030041:Hepatitis A virus / Q000276:immunology; D018928:Immunity, Mucosal; D007114:Immunization; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D013107:Sphingolipids / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D002412:Cations; D035922:Hepatitis A Antibodies; D022362:Hepatitis A Vaccines; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D013107:Sphingolipids; D002784:Cholesterol