Development of a multivalent (pan-firovirus) vaccine for filoviruses (Zaire, Sudan, Bundibugyo, Marburg) using a virus-like particle (VLP) platform.
The development of multivalent vaccines against four major filovirus strains (Zaire, Sudan, Bundibugyo, and Marburg) using a virus-like particle (VLP) platform is considered highly promising as an approach that can achieve both "safety without using live viruses" and "potent immune induction ability that closely resembles real viruses." Because it contains absolutely no viral RNA genes, it cannot replicate in the body. This completely eliminates the side effects (fever and joint pain) and the risks associated with administering it to immunocompromised patients that are a concern with replicating vector vaccines such as rVSV.
1️⃣Basic structure of VLP polyvalent vaccines
Filovirus VLPs (Very Large Liposuction Cells) are spontaneously assembled within the cell by simultaneously producing the matrix protein (VP40) that forms the viral skeleton and the "target antigen." Just like real viruses form spores, hollow lipid bilayer particles (VLPs) are automatically formed and released outside the cell.
2️⃣Designing "diversification"
When creating a multivalent vaccine that covers all four viruses, two designs are employed: the mosaic (hybrid) VLP approach and the cocktail VLP approach. The mosaic (hybrid) VLP approach involves simultaneously displaying all four glycoproteins (GPs) of the Zaire strain (EBOV), Sudan strain (SUDV), Bundibugyo strain (BDBV), and Marburg virus (MARV) on the surface of a single VLP. The cocktail VLP approach involves separately manufacturing monovalent VLPs corresponding to each strain (e.g., a VLP with the Zaire strain GP, a VLP with the Marburg strain GP) and then blending them evenly to create a single formulation.Technical challenges
3️⃣Technical challenges
Control of immune dominance and interference is necessary. For example, when four GPs are mixed, the immune response to, for instance, the "Zaire strain GP" may become stronger, while antibody production against the "Bundibugyo strain" and the "Marburg strain" is suppressed (immune interference). To prevent this, research is underway to optimize the mixing ratio of each GP and to modify the sugar chains to highlight common structures (immunofocusing). Other mechanisms of immune interference also exist.
Because VLPs are structures with complex envelopes (lipid membranes), they cannot be produced in E. coli and other bacteria, requiring expensive culture and purification processes using mammalian cells (such as HEK293) or insect cells (baculovirus systems).
4️⃣Issues that CEPI is already supporting with the VLP platform.
A leading project for multivalent filovirus vaccines, supported by CEPI (Coalition for Epidemic Preparedness Innovations) in collaboration with the European Union's Horizon Europe program using a virus-like particle (VLP) platform, is an international consortium project led by AdaptVac (Denmark).
The leading organization is AdaptVac (a Danish biotechnology company), and the project is part of a global research consortium that includes collaborating institutions such as Wageningen University & Research (Netherlands) and the Lambaréne Medical Research Centre (Gabon). The funding scale is up to $12.4 million. The core approach of this project is AI-powered antigen (immunogen) design. Rather than simply mixing in wild-type sequences, they use AI technology to design optimal artificial antigens that target regions common to filoviridae (such as Zaire strains, Sudan strains, and Marburg virus) to achieve broad protective effects (cross-protection). The designed antigens are bound to AdaptVac's proprietary high-density capsid-VLP (virus-like particle) platform, in which AdaptVac has a strong advantage. This creates an "all-in-one" vaccine candidate that covers multiple deadly filoviruses with a single vaccine particle. After confirming efficacy and safety in preclinical trials, plans are underway to conduct Phase 1/2 clinical trials in Gabon and the Netherlands.
＊The illustration was drawn by Nano Banana 2 of Gemini. Thanks !
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