The main objective of the MACIVIVA European consortium was to develop new Good Manufacturing Practice pilot lines for manufacturing thermostable vaccines with stabilized antigens on influenza virosomes as enveloped virus-like particles. The HIV-1 gp41-derived antigens anchored in the virosome membrane, along with the adjuvant 3M-052 (TLR7/8 agonist) on the same particle, served as a candidate vaccine for the proof of concept for establishing manufacturing processes, which can be directly applied or adapted to other virosomal vaccines or lipid-based particles. Heat spray-dried powders suitable for nasal or oral delivery, and freeze-dried sublingual tablets were successfully developed as solid dosage forms for mucosal vaccination. The antigenic properties of vaccinal antigens with key gp41 epitopes were maintained, preserving the original immunogenicity of the starting liquid form, and also when solid forms were exposed to high temperature (40°C) for up to 3 months, with minimal antigen and adjuvant content variation. Virosomes reconstituted from the powder forms remained as free particles with similar size, virosome uptake by antigen-presenting cells in vitro was comparable to virosomes from the liquid form, and the presence of excipients specific to each solid form did not prevent virosome transport to the draining lymph nodes of immunized mice. Virosome integrity was also preserved during exposure to <−15°C, mimicking accidental freezing conditions. These "ready to use and all-in-one" thermostable needle-free virosomal HIV-1 mucosal vaccines offer the advantage of simplified logistics with a lower dependence on the cold chain during shipments and distribution.
Abbreviations: Hydroxypropyl methylcellulose (HPMC), polyethylene oxide (PEO), Magnetic resonance imaging (MRI).
Abstract PurposeInvestigate the extended release behaviour of compacts containing mixtures of hydrophilic HPMC and PEO in hydrating media of differing ionic strengths.
MethodsThe extended release behaviour of various HPMC:PEO compacts was investigated using dissolution testing, confocal microscopy and magnetic resonance imaging, with respect to polymer ratio and ionic strength of the hydrating media.
ResultsIncreasing HPMC content gave longer extended release times, but a greater sensitivity to high ionic dissolution environments. Increasing PEO content reduced this sensitivity. The addition of PEO to a predominantly HPMC matrix reduced release rate sensitivity to high ionic environments. Confocal microscopy of early gel layer development showed the two polymers appeared to contribute independently to gel layer structure whilst together forming a coherent and effective diffusion barrier. There was some evidence that poorly swollen HPMC particles added a tortuosity barrier to the gel layer in high ionic strength environments, resulting in prolonged extended release. MRI provides unique, non-invasive spatially resolved information from within the HPMC:PEO compacts that furthers our understanding of USP 1 and USP 4 dissolution data.
ConclusionsConfocal microscopy and MRI data show that combinations of HPMC and PEO have advantageous extended release properties, in comparison with matrices containing a single polymer.
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