The concomitant use of the LTK63 mucosal adjuvant and of chitosan-based delivery system enhances the immunogenicity and efficacy of intranasally administered vaccines

Barbara C Baudner; Marzia M Giuliani; J Coos Verhoef; Rino Rappuoli; Hans E Junginger; Giuseppe Del Giudice

doi:10.1016/s0264-410x(03)00305-0

The concomitant use of the LTK63 mucosal adjuvant and of chitosan-based delivery system enhances the immunogenicity and efficacy of intranasally administered vaccines

Vaccine. 2003 Sep 8;21(25-26):3837-44. doi: 10.1016/s0264-410x(03)00305-0.

Authors

Barbara C Baudner¹, Marzia M Giuliani, J Coos Verhoef, Rino Rappuoli, Hans E Junginger, Giuseppe Del Giudice

Affiliation

¹ IRIS Research Center, Chiron SpA, Via Fiorentina 1, 53100 Siena, Italy.

PMID: 12922117
DOI: 10.1016/s0264-410x(03)00305-0

Abstract

In this paper we evaluated chitosan microparticles as a vaccine delivery system as well as the mucosal adjuvant LTK63, a nontoxic Escherichia coli enterotoxin (LT) mutant for the intranasal immunization with the group C meningococcal conjugated vaccine (CRM-MenC). Mice receiving intranasally the CRM-MenC vaccine formulated with chitosan microparticles and the LTK63 mutant showed higher titers of systemic and mucosal antibodies specific for the group C meningococcal polysaccharide as compared to those receiving the vaccine subcutaneously. In addition, high bactericidal activity was found in serum samples of mice immunized intranasally with the conjugated vaccine formulated together with the microparticles and the LT mutant. These results demonstrate that the concomitant use of chitosan microparticles and the LTK63 mutant significantly enhances the immunogenicity and the protective efficacy of vaccines given intranasally.

MeSH terms

Adjuvants, Immunologic / pharmacology*
Administration, Intranasal
Animals
Antibodies, Bacterial / analysis
Antibodies, Bacterial / biosynthesis
Bacterial Toxins / pharmacology*
Bacterial Vaccines / immunology
Chemistry, Pharmaceutical
Chitin / analogs & derivatives*
Chitin / pharmacology*
Chitosan
Diphtheria Toxin / immunology
Diphtheria Toxin / pharmacology
Drug Delivery Systems
Enterotoxins / pharmacology*
Enzyme-Linked Immunosorbent Assay
Escherichia coli Proteins*
Excipients
Female
Immunization
Immunoglobulin A / biosynthesis
Immunoglobulin A / immunology
Immunoglobulin G / biosynthesis
Immunoglobulin G / immunology
Mice
Mice, Inbred BALB C
Microspheres
Neisseria meningitidis, Serogroup C / immunology
Vaccines / administration & dosage*
Vaccines / immunology*

Substances

Adjuvants, Immunologic
Antibodies, Bacterial
Bacterial Toxins
Bacterial Vaccines
Diphtheria Toxin
Enterotoxins
Escherichia coli Proteins
Excipients
Immunoglobulin A
Immunoglobulin G
Vaccines
Chitin
Chitosan
heat-labile enterotoxin, E coli