Relationship between structure and adjuvanticity of N,N,N-trimethyl chitosan (TMC) structural variants in a nasal influenza vaccine
| Autor: | Pascal H.J.L.F. de Jong, Niels Hagenaars, Enrico Mastrobattista, J.G.M. Heldens, Harrie L. Glansbeek, Rolf J. Verheul, Imke Mooren, Wim E. Hennink, Han van den Bosch, Wim Jiskoot |
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| Rok vydání: | 2009 |
| Předmět: |
Time Factors
Influenza vaccine Chemistry Pharmaceutical Drug Compounding medicine.medical_treatment Orthomyxoviridae Pharmaceutical Science Antibodies Viral Methylation Microbiology Chitosan Mice Structure-Activity Relationship chemistry.chemical_compound Adjuvants Immunologic Orthomyxoviridae Infections Adjuvanticity Animals Medicine Administration Intranasal Immunization Schedule Molecular Structure biology business.industry Immunogenicity Antibody titer Acetylation Nasal Lavage Fluid biology.organism_classification Molecular biology Mice Inbred C57BL Disease Models Animal Vaccines Inactivated chemistry Influenza A virus Influenza Vaccines Immunoglobulin G Immunoglobulin A Secretory Female Nasal administration business Adjuvant |
| Zdroj: | Journal of Controlled Release. 140:126-133 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2009.08.018 |
| Popis: | The aim of this study was to assess the influence of structural properties of N,N,N-trimethyl chitosan (TMC) on its adjuvanticity. Therefore, TMCs with varying degrees of quaternization (DQ, 22-86%), O-methylation (DOM, 0-76%) and acetylation (DAc 9-54%) were formulated with whole inactivated influenza virus (WIV). The formulations were characterized physicochemically and evaluated for their immunogenicity in an intranasal (i.n.) vaccination/challenge study in mice. Simple mixing of the TMCs with WIV at a 1:1 (w/w) ratio resulted in comparable positively charged nanoparticles, indicating coating of WIV with TMC. The amount of free TMC in solution was comparable for all TMC-WIV formulations. After i.n. immunization of mice with WIV and TMC-WIV on days 0 and 21, all TMC-WIV formulations induced stronger total IgG, IgG1 and IgG2a/c responses than WIV alone, except WIV formulated with reacetylated TMC with a DAc of 54% and a DQ of 44% (TMC-RA44). No significant differences in antibody titers were observed for TMCs that varied in DQ or DOM, indicating that these structural characteristics play a minor role in their adjuvant properties. TMC with a DQ of 56% (TMC56) formulated with WIV at a ratio of 5:1 (w/w) resulted in significantly lower IgG2a/c:IgG1 ratios compared to TMC56 mixed in ratios of 0.2:1 and 1:1, implying a shift towards a Th2 type immune response. Challenge of vaccinated mice with aerosolized virus demonstrated protection for all TMC-WIV formulations with the exception of TMC-RA44-WIV. In conclusion, formulating WIV with TMCs strongly enhances the immunogenicity and induces protection against viral challenge in mice after i.n. vaccination. The adjuvant properties of TMCs as i.n. adjuvant are strongly decreased by reacetylation of TMC, whereas the DQ and DOM hardly affect the adjuvanticity of TMC. |
| Databáze: | OpenAIRE |
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