Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 539205
Title Development of a Virosomal RSV Vaccine Containing 3D-PHAD® Adjuvant : Formulation, Composition, and Long-Term Stability
Author(s) Lederhofer, J.; Lent, J. van; Bhoelan, F.; Karneva, Z.; Haan, A. de; Wilschut, J.C.; Stegmann, T.
Source Pharmaceutical Research 35 (2018)9. - ISSN 0724-8741
DOI https://doi.org/10.1007/s11095-018-2453-y
Department(s) Laboratory of Virology
EPS
Publication type Refereed Article in a scientific journal
Publication year 2018
Keyword(s) adjuvant - monophosphoryl lipid A - respiratory syncytial virus - single particle tracking - vaccine - virosomes
Abstract

Purpose: Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHAD® adjuvant. Methods: Virosomes were initially formed by contacting a lipid film containing 3D-PHAD® with viral membranes solubilized with the short chain phospholipid DCPC, followed by dialysis, later by adding solubilized 3D-PHAD to viral membranes, or to preformed virosomes from DMSO. Results: Virosomes formed from lipid films contained the membrane glycoproteins G and F, at similar F to G ratios but lower concentrations than in virus, and the added lipids, but only a fraction of the 3D-PHAD®. By single particle tracking (SPT), the virosome size distribution resembled that seen by cryo-electron microscopy, but dynamic light scattering showed much larger particles. These differences were caused by small virosome aggregates. Measured by SPT, virosomes were stable for 300 days. 3DPHAD ® incorporation in virosomes could be enhanced by providing the adjuvant from DCPC solubilized stock, but also by adding DMSO dissolved adjuvant to pre-formed virosomes. Virosomes with 0.1 mg/mg of 3D-PHAD®/viral protein from DMSO induced antibody titers similar to those by virosomes containing 0.2 mg/mg of DCPC-solubilized 3D-PHAD®. Conclusions: Stable 3D-PHAD® adjuvanted RSV virosomes can be formulated.

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