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Development of a Virosomal RSV Vaccine Containing 3D-PHADA (R) Adjuvant: Formulation, Composition, and Long-Term Stability

Lederhofer, J., van Lent, J., Bhoelan, F., Karneva, Z., de Haan, A., Wilschut, J. C. & Stegmann, T., Sep-2018, In : Pharmaceutical Research. 35, 9, 14 p., 172.

Research output: Contribution to journalArticleAcademicpeer-review

Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHADA (R) adjuvant.

Virosomes were initially formed by contacting a lipid film containing 3D-PHADA (R) 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.

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-PHADA (R). 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 A (R) 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-PHADA (R)/viral protein from DMSO induced antibody titers similar to those by virosomes containing 0.2 mg/mg of DCPC-solubilized 3D-PHADA (R).

Stable 3D-PHADA (R) adjuvanted RSV virosomes can be formulated.

Original languageEnglish
Article number172
Number of pages14
JournalPharmaceutical Research
Volume35
Issue number9
Publication statusPublished - Sep-2018

    Keywords

  • adjuvant, monophosphoryl lipid A, respiratory syncytial virus, single particle tracking, vaccine, virosomes, RESPIRATORY-SYNCYTIAL-VIRUS, MONOPHOSPHORYL-LIPID-A, DYNAMIC LIGHT-SCATTERING, T-CELL RESPONSE, FUSION GLYCOPROTEIN, ENHANCED DISEASE, COTTON RATS, PROTEIN, ANTIBODIES, INFECTION

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