Periodic Reporting for period 3 - MACIVIVA (MAnufacturing process for Cold-chain Independent VIrosome-based VAccines)
Reporting period: 2017-11-04 to 2018-11-03
Virosome-based vaccines are generally under liquid form and as any liquid vaccine they contain a lot of water. Consequently, such vaccines are susceptible to instability due to vulnerability to accidental freezing or exposure to high temperature (> 35oC) during storage or transportation, leading to irreversible damages to the virosomal vaccines. Furthermore, chemical modifications may take place in the liquid vaccine (ex. product oxidation), and increase the risk of unwanted side effects. These scenarios frequently happen during vaccine shipment to warm countries. Therefore, maintenance of the cold chain at the right temperature is fundamental for preserving the vaccine bioactivity. However, such infrastructures are absent or inadequate in many developing countries, and it increases the risk of losing vaccines or rendering them less efficacious.
To prevent or reduce chemical modifications and improve the vaccine thermostability in case of exposure to low and high temperatures, removing most of the water from the virosome-based vaccines to generate needle-free vaccines under various powder forms with low moisture content (< 5% water) was identified as a promising approach.
This led to the set-up of the MACIVIVA (Manufacturing process for cold-chain Independent Virosome-based Vaccines) consortium in 2015 supported by the EU Horizon 2020 and the Swiss government (grant agreement No 646122). For achieving the project objectives, MACIVIVA involved collaborators with expertise and manufacturing capabilities in heat spray-drying (Upperton Ltd) or freeze/freeze drying also known as lyophilisation (Catalent UK Swindon Zydis Ltd) that could be applied to virosomes as vaccinal antigen carrier (Mymetics SA/BV) for generating new solid vaccine dosages. Other collaborators joined the consortium for providing their expertise and manufacturing capabilities either for the vaccinal synthetic P1 peptide (Bachem AG) or the recombinant gp41 HIV-1 protein produced in bacteria (subcontracted to Px’Therapeutics). These new solid vaccine forms were used for vaccinating animals for confirming that that they have retained their ability to induce antibodies. For evaluating the vaccine-induced antibody responses in the blood and mucosal secretions from various tissues (genital, rectal, nasal and lungs), the detection of antibodies was performed by the partner with the expertise in the development of innovative antibody quantification assays (Chimera Biotec GmbH). MACIVIVA project ended in early November 2018 after 42 months of outstanding collaborations between the six Consortium partners and a dozen of subcontractors, achieving all the objectives. Three new GMP Pilot Lines are now available in Europe for manufacturing virosomal vaccines as spray-dried nasal and oral powders and lyophilized sublingual tablets.
By the end of MACIVIVA in month 42 (November 3rd 2018), the consortium successfully achieved all the main objectives, with the 24 Deliverables initially planned that were completed and submitted to the European Commission. There were also eight Milestones that were successfully achieved, with the establishment and completion of the three GMP Pilot Lines with their corresponding GMP vaccine lots with a promising thermostable and immunogenic HIV-1 vaccine candidate as end-product. These new solid vaccine forms are making the virosome technology more attractive and competitive, and it opens the door to other future therapeutic and prophylactic vaccines based on virus-like particles, improving also the European competitiveness with this nanovaccine manufacturing technology.
Furthermore, with “ready-to use” vaccine solid dosage forms, there is no more need to provide needles and vials with diluents for vaccine reconstitution, rendering vaccine handling safer with a simplified logistics. Mucosal vaccinations are non-invasive and painless, favoring a broader population acceptance. They are expected to elicit mucosal immunity in the genital and rectal tract, the main entry doors of HIV-1 and many other pathogens, offering improved protection against sexually transmitted pathogens, as compared to vaccines inducing only blood immune responses for preventing mucosally transmitted pathogens.
Other existing virosomal vaccines or other vaccines obtained by different technologies could benefit from MACIVIVA Pilot Lines and acquired know-how. Due to the ease of mucosal administration of solid vaccine forms, gradual replacement of liquid and lyophilized/reconstituted vaccines by needle-free vaccines is expected, favoring higher immunization coverage for the great benefit of the overall health care system. MACIVIVA results may raise high interest from major stakeholders, increase the European attractiveness as location of choice to carry-out thermostable vaccine development, promise sustainability and creation of high tech jobs and leverage investments.