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Monday, August 13, 2018 9:47:54 PM
PAPER
Development of a Virosomal RSV Vaccine Containing
3D-PHAD® Adjuvant: Formulation, Composition,
and Long-Term Stability
J. Lederhofer
1&J. van Lent
2
&F. B h o e l a n
3
&Z. Karneva
3
&A. de Haan
1
&J.C. Wilschut &
T. Stegmann
3
Received: 1 May 2018 /Accepted: 26 June 2018
#The Author(s) 2018
ABSTRACT
Purpose Characterization of virosomes, in late stage preclin-
ical 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 solu-
bilized with the short chain phospholipid DCPC, followed by
dialysis, later by adding solubilized 3D-PHAD to viral mem-
branes, 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 anti-
body 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
(PDF) Development of a Virosomal RSV Vaccine.... Available from: https://www.researchgate.net/publication/326166555_Development_of_a_Virosomal_RSV_Vaccine_Containing_3D-PHADR_Adjuvant_Formulation_Composition_and_Long-Term_Stability [accessed Aug 13 2018].
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