NDLI: Physicochemical and Immunological Characterization of N,N,N-Trimethyl Chitosan-Coated Whole Inactivated Influenza Virus Vaccine for Intranasal Administration

Content Provider	Springer Nature Link
Author	Hagenaars, Niels Mastrobattista, Enrico Verheul, Rolf J. Mooren, Imke Glansbeek, Harrie L. Heldens, Jacco G. M. Bosch, Han Jiskoot, Wim
Copyright Year	2009
Abstract	The purpose of this study was the development and physicochemical and immunological characterization of intranasal (i.n.) vaccine formulations of whole inactivated influenza virus (WIV) coated with N,N,N-trimethyl chitosan (TMC).Synthesized TMCs with a degree of quarternization of 15% (TMC15) or 37% (TMC37) were tested in vitro for their ability to decrease the transepithelial resistance (TEER) of an epithelial cell monolayer. TMC15- and TMC37-coated WIV (TMC15-WIV and TMC37-WIV) were characterized by zeta potential measurements, dynamic light scattering, electron microscopy and gel permeation chromatography. Mice were vaccinated i.n. with selected vaccine formulations and immunogenicity was determined by measuring serum hemagglutination inhibition (HI) and serum IgG, IgG1 and IgG2a/c titers. Also a pulse-chase study with TMCs in solution administered i.n. 2 h prior to WIV was performed. Protective efficacy of vaccination was determined by an aerosol virus challenge.TMC37 induced a reversible decrease in TEER, suggesting the opening of tight junctions, whereas TMC15 did not affect TEER. Simple mixing of (negatively charged) WIV with TMC15 or TMC37 resulted in positively charged particles with TMCs being partially bound. Intranasal immunization with TMC37-WIV or TMC15-WIV induced stronger HI, IgG, IgG1 and IgG2a/c titers than WIV alone. TMC37-WIV induced the highest immune responses. Both TMC15-WIV and TMC37-WIV provided protection against challenge, whereas WIV alone was not protective. Intranasal administration of TMC prior to WIV did not result in significant immune responses, indicating that the immunostimulatory effect of TMC is primarily based on improved i.n. delivery of WIV.Coating of WIV with TMC is a simple procedure to improve the delivery and immunogenicity of i.n. administered WIV and may enable effective i.n. vaccination against influenza.
Starting Page	1353
Ending Page	1364
Page Count	12
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	26
Issue Number	6
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2009-02-18
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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