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Title: Intranasal chitosan-DNA vaccines that protect across influenza virus subtypes
Authors: Chompoonuch Sawaengsak
Yasuko Mori
Koichi Yamanishi
Potjanee Srimanote
Wanpen Chaicumpa
Ampol Mitrevej
Nuttanan Sinchaipanid
Mahidol University
National Institute of Biomedical Innovation
Kobe University School of Medicine
Thammasat University
Keywords: Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Oct-2014
Citation: International Journal of Pharmaceutics. Vol.473, No.1-2 (2014), 113-125
Abstract: An egg-free and broadly effective influenza vaccine that can be produced rapidly, adequately and cost-effectively is needed. In this study, chitosan-associated DNAs prepared at various nitrogen/phosphate charge (N/P) ratios were studied for their physicochemical properties, stability, cytotoxicity, and protein expression ability. The chitosan-DNA complexes (chitoplexes) of the N/P ratio 2 had the required characteristics including optimal size range, positive surface charge, high DNA association efficiency, tolerability to DNase digestion and mammalian cell viability compatibility. The N/P ratio 2-chitoplexes revealed the highest green fluorescent protein and luciferase expressions in the transfected mammalian cell cultures and in the mouse lungs. Mice immunized intranasally with the N/P ratio 2-chitoplex vaccines carrying DNAs coding for conserved proteins of influenza virus, i.e., ion channel protein (M2) and/or nucleoprotein (NP), had both mucosal and systemic humoral as well as cell mediated immune responses to the in vivo expressed antigens which conferred protection in mice against the lethal challenges not only with the homologous influenza virus subtype (H1N1), but also the heterologous subtype (H3N2). The chitoplexes should be considered as influenza vaccine candidates especially during the period of high vaccine demand. They are suitable for developing areas of the world where conventional vaccine production capacity is lacking. © 2014 Elsevier B.V.
ISSN: 18733476
Appears in Collections:Scopus 2011-2015

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