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Cationic liposomes as adjuvants for influenza hemagglutinin: more than charge alone.

Abstract
Cationic liposomes are known as potent adjuvants for subunit vaccines. The purpose of this work was to study whether the content and the physicochemical properties of the positively charged compound affect the adjuvanticity of cationic liposomes. Cationic liposomes containing a cationic compound (DDA, DPTAP, DC-Chol, or eDPPC) and a neutral phospholipid (DPPC) were prepared by the film hydration-extrusion method and loaded with influenza hemagglutinin (HA) by adsorption. The liposomes were characterized (hydrodynamic diameter, zeta potential, membrane fluidity, HA loading) and their adjuvanticity was tested in mice. The formulations were administered twice subcutaneously and mouse sera were analyzed for HA-specific antibodies by ELISA and for HA-neutralizing antibodies by hemagglutination inhibition (HI) assay. First, the influence of cationic lipid concentration in the DC-Chol/DPPC liposomes (10 vs. 50 mol%) was investigated. The DC-Chol/DPPC (50:50) liposomes showed a higher zeta potential and HA loading, resulting in stronger immunogenicity of the HA/DC-Chol/DPPC (50:50) liposomes compared to the corresponding (10:90) liposomes. Next, we used liposomes composed of 50 mol% cationic lipids to investigate the influence of the nature of the cationic compound on the adjuvant effect. Liposomes made of the four cationic compounds showed similar hydrodynamic diameters (between 100 and 170 nm), zeta potentials (between +40 and +50 mV), HA loading (between 55% and 76%) and melting temperatures (between 40 and 55 °C), except for the DC-Chol liposomes, which did not show any phase transition. HA adjuvanted with the DC-Chol/DPPC (50:50) liposomes elicited significantly higher total IgG1 and IgG2a titers compared to the other liposomal HA formulations and non-adjuvanted HA. A similar trend was observed for the HI titers. These results show that the adjuvanticity of cationic liposomes depends on both the content and the physicochemical properties of the charged compound.
AuthorsChristophe Barnier Quer, Abdelrahman Elsharkawy, Stefan Romeijn, Alexander Kros, Wim Jiskoot
JournalEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 81 Issue 2 Pg. 294-302 (Jun 2012) ISSN: 1873-3441 [Electronic] Netherlands
PMID22487055 (Publication Type: Journal Article)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Adjuvants, Immunologic
  • Cations
  • Hemagglutinins
  • Influenza Vaccines
  • Lipids
  • Liposomes
  • Phospholipids
Topics
  • Adjuvants, Immunologic (chemistry)
  • Animals
  • Cations (chemistry, immunology)
  • Chemistry, Pharmaceutical (methods)
  • Female
  • Hemagglutination Inhibition Tests (methods)
  • Hemagglutinins (chemistry, immunology)
  • Influenza Vaccines (chemistry, immunology)
  • Lipids (chemistry, immunology)
  • Liposomes (chemistry, immunology)
  • Membrane Fluidity (immunology)
  • Mice
  • Mice, Inbred C57BL
  • Particle Size
  • Phase Transition
  • Phospholipids (chemistry, immunology)

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