New GMP manufacturing processes to obtain thermostable HIV-1 gp41 virosomes under solid forms for various mucosal vaccination routes.
Mario AmackerCharli SmardonLaura MasonJack SorrellKirk JefferyMichael AdlerFarien BhoelanOlga BelovaMark SpenglerBeena PunnamoottilMarkus SchwallerOlivia BonduelleBehazine CombadièreToon StegmannAndrew NaylorRichard JohnsonDesmond WongSylvain FleuryPublished in: NPJ vaccines (2020)
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.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- lymph node
- men who have sex with men
- early stage
- high temperature
- dendritic cells
- ulcerative colitis
- induced apoptosis
- healthcare
- immune response
- primary care
- ionic liquid
- type diabetes
- randomized controlled trial
- toll like receptor
- escherichia coli
- cell cycle arrest
- clinical trial
- fatty acid
- signaling pathway
- ultrasound guided
- high fat diet induced
- high density
- study protocol
- heat stress
- candida albicans
- endoplasmic reticulum stress
- biofilm formation