Immune Modulation by Adjuvants Combined with Diphtheria Toxoid Administered Topically in BALB/c Mice After Microneedle Array Pretreatment

• Published in: Pharmaceutical research Vol. 26; no. 7; pp. 1635 - 1643
• Main Authors: Ding, Z, Van Riet, E, Romeijn, S, Kersten, G. F. A, Jiskoot, W, Bouwstra, J. A
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.07.2009; Springer US; Springer; Springer Nature B.V
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Cutaneous; Animals; Antibody Formation - drug effects; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; cholera toxin; Cholera Toxin - administration & dosage; Cholera Toxin - immunology; CpG; Diphtheria; diphtheria toxoid; Diphtheria Toxoid - administration & dosage; Diphtheria Toxoid - immunology; Drug delivery systems; Female; General pharmacology; Immune system; Immunization; Immunization - instrumentation; Immunization - methods; Immunoglobulin G - blood; Immunoglobulin G - immunology; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - immunology; Medical Law; Medical sciences; Mice; Mice, Inbred BALB C; microneedle array; Oligodeoxyribonucleotides - administration & dosage; Oligodeoxyribonucleotides - immunology; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Quillaja Saponins; Research Paper; Respiratory diseases; Saponins - administration & dosage; Saponins - immunology; transcutaneous immunization; Vaccines; microneedle array; CpG; transcutaneous immunization; cholera toxin; diphtheria toxoid; Immunization; Pharmaceutical technology; Toxoid; Rodentia; Diphtheria; Percutaneous route; Infection; Toxin; Vertebrata; Mammalia; Mouse; Animal; Bacteriosis; Adjuvant; Cholera; Pretreatment; Microneedle; Topical administration
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-009-9874-6

Purpose In this study, modulation of the immune response against diphtheria toxoid (DT) by various adjuvants in transcutaneous immunization (TCI) with microneedle array pretreatment was investigated. Methods TCI was performed on BALB/c mice with or without microneedle array pretreatment using DT as a model antigen co-administrated with lipopolysaccharide (LPS), Quil A, CpG oligo deoxynucleotide (CpG) or cholera toxin (CT) as adjuvant. The immunogenicity was evaluated by measuring serum IgG subtype titers and neutralizing antibody titers. Results TCI with microneedle array pretreatment resulted in a 1,000-fold increase of DT-specific serum IgG levels as compared to TCI. The immune response was further improved by co-administration of adjuvants, showing a progressive increase in serum IgG titers when adjuvanted with LPS, Quil A, CpG and CT. IgG titers of the CT-adjuvanted group reached levels comparable to those obtained after DT-alum subcutaneous injection. The IgG1/IgG2a ratio of DT-specific antibodies decreased in the following sequence: plain DT, Quil A, CT and CpG, suggesting that the immune response was skewed towards the Th1 direction. Conclusions The potency and the quality of the immune response against DT administered by microneedle array mediated TCI can be modulated by co-administration of adjuvants.