- Imperial College London
- Bristol University
- LMIC partners
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Challenge and opportunity
The Baculovirus/insect cell system (BICS) is a highly efficient production tool to manufacture complex protein biologics. BICS has been used successfully to produce vaccines against HPV, the virus that causes cervical cancer (eg. Gardasil®). The Bristol group have developed MultiBac that is optimized, engineered baculoviral system to produce complex biologics including next-generation vaccines.
The MultiBac platform shall be used to produce next-generation vaccine candidates to combat emerging infectious diseases in partnership with other Hub partners in LMIC. These vaccine candidates will include specimens based on Bristol group’s proprietary ADDomerTM technology.
The ADDomer technology is particularly suited for native-like display of immunogenic epitopes at high copy-number on the surface of this highly soluble nanoparticle, eliciting impressively high immune responses against key vaccine candidate antigens.
Insect cells are grown to high density using GMP-compatible procedures and infected with recombinant MultiBac Baculo-viruses encoding for the vaccine candidates of choice. Protein particles are purified either from the culture supernatant (eg. membrane enveloped virus-like particles VLPs) or from the cytoplasmic (nanoparticles including ADDomer). This methodology will theoretically enable expression of the entire universe of existing immunogenic epitopes from pathogens, viral and bacterial.
The Bristol group have produced Non-cGMP and cGMP lots of a) Chikungunya; b) Zika and c) combo Chigungunya-Zika nanoparticle-based vaccine candidates and developed a range of analytical methods including electron cryo-microscopy to quality control each preparations. Moreover, in the Hub we are developing sophisticated algorithms to simulate and predict manufacturing costs and identify opportunities to further economize the processes through modularization for ease of implementation, especially in an LMIC setting.
A vital asset of our nano-particle is its remarkable thermotolerance, making its storage, transport and deployment independent of a cold chain. Key outcomes are listed below.
Key outcomes form this workstream
- Produce and evaluate a range of powerful vaccine candidates using the MultiBac/BICS
- Develop a multi-disease approach to ADDomer based vaccines
- Develop predictive process algorithms to simulate MultiBac-based manufacture
- Evaluate ADDomer-based vaccines for oral delivery
- Create library-based approaches for next-generation ADDomer-based vaccines
- Implement modular manufacturing process and robust QA