WP3 aims at developing innovative formulations and processes compatible with antigens, adjuvants and stabilizers in the various vaccines. Formulation needs to result in stable vaccines suitable for the intended route of administration.
Three dry powder formulations were proposed to carry a promising vaccine against influenza, conformed by four different peptides. These formulations are based on spray dry technology and stabilization with sugar glass technology. SD Lys-P showed to have high stability, allowing the storage of the vaccine at room temperature. Moreover, due to its physical characteristics and particle size, it could be administrated by inhalation, potentiating its action by taking advantage of the immune system of the respiratory tract. In order to increase the immunogenicity of the product, the adjuvant MPLA was incorporated within the formulation of the lysine modified peptides (SD Lys-P-MPLA). Through in vitro studies it could be verified that the adjuvant was incorporated into the final product with remaining activity after the after spray drying process. This result shows that it is feasible to include an adjuvant such as MPLA within spray dried formulations without affecting its function.
When investigating the freeze dried M-001 antigen, stability tests showed that M-001 did not significantly change in particle size after being freeze dried with trehalose, inulin or a combination of trehalose with dextran (1:1) and stored for 16 days at 5 and 30°C. Inulin and trehalose seem suitable stabilizing agents. Based on the seroconversion results in which a freeze dried formulation of M-001 with trehalose was used, this formulation seems promising to be further used in preclinical testing and perhaps clinical testing.
In vitro studies on whole inactivated virus (WIV) vaccine revealed interaction of the vaccine with the liposomal adjuvant CAF01, especially at higher WIV/CAF01 ratios. Freeze-drying of WIV together with CAF01, CAF09, CTA1DD, or CTA1-3M2e-DD (the adjuvants present in the UNISEC consortium) resulted in stable but partly insoluble cakes (CAF01, CAF09) or physically instable cakes (CTA1-containing adjuvants). Strategies were developed to improve solubility and stability of these cakes.
Recent data from the consortium has shown that the emulsion based adjuvant Diluvac Forte® also incorporating alpha-tocopherol has the ability to enhance the immunogenicity of a naked DNA vaccine. The purpose of this particular study was therefore to make emulsion delivery systems similar to Diluvac Forte® incorporating different concentrations of alpha-tocopherol in order to test the role of alpha-tocopherol in immunogenicity of the plasmid DNA. Formulations of paraffin oil/polysorbat based emulsions were formulated where paraffin oil were gradually (up to 75%) replaced with alpha-tocopherol. Emulsions were prepared by microfluidization. The formulations are currently being evaluated in murine studies.
wp3. UNISEC poster formulation and administration new.ppt
4/15/2016 9:13:46 AM