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Gas Vesicles (GV)


Gas vesicles are fascinating protein nanostructures found in some bacteria and archaea. These hollow organelles function like tiny balloons, helping these microbes achieve buoyancy control in aquatic environments. The protein shell of GV is incredibly strong and permeable only to gas, but not water.

Gas vesicles are cylindrical or spindle-shaped nano-structures composed entirely of protein. The diameter of GV is 40-100 nm and the length is 100-1000 nm. No DNA/RNA, lipids or carbohydrates are found in the purified GV.

Imaged by Willem Noteborn

Gas vesicles mainly consist of a single structure protein, GvpA. This 70-90 amino acid long hydrophobic protein forms the ribs of the GVs. 

A scaffold protein, GvpC, is found in some GV in haloarchaea and cyanobacteria. GvpC binds to the outside of the GvpA ribs through protein-protein interaction and helps maintain the shape and rigidity of the vesicle. 

Chimeric Gas Vesicles (CGVs)

Chimeric gas vesicles are recombinant gas vesicles which involve two different GvpAs, we call the major GvpA and minor GvpA’. The major GvpA can form GV alone, while minor GvpA’ can form GV only when GvpA are present. Both GvpA and GvpA’ form the ribs of the vesicle. 

The ratio of GvpA’:GvpA is about 1:4 to 1:8. 

The heterogeneous peptide up to 62 amino acids long can be fused to GvpA’ and CGVs are formed. 

CGVs offer a compelling alternative to traditional vaccine platforms with several key advantages

The future trend of vaccine development is mRNA vaccines and subunit (protein) vaccines. CGV Vaccine has its advantage over other vaccine platforms and could be the best choice in the subunit vaccine field based on the following reason:

  1. Pure protein nanostructure: CGV is 100% pure protein nanostructure without DNA/RNA, lipids or carbohydrates.

  2. Self-adjuvant: No need for adjuvant due to its nanostructure, though GvpA itself is not immunogenic. These potentially lead to a safer profile of the vaccine platform.

  3. Strong immune response: Like VLPs, CGVs present antigen fragments on their surface, stimulating both mucosal and systemic immune responses.

  4. High epitope ratio: A high proportion of the foreign epitope displayed on the CGV surface could potentially enhance immune response. A 50-AA heterogeneous epitope accounts roughly 7-12% of total CGV protein.

  5. Versatile Delivery: CGVs can be administered via various routes including nasal spray, oral, or subcutaneous injection.

  6. Potential for mucosal immunity: Nasally delivered CGV vaccines might offer protection by neutralizing viruses at the point of entry (respiratory tract) through secretory IgA (SIgA) antibodies.

  7. Broad Applicability: With flexible epitope selection for various pathogens (up to 62 amino acids), CGVs hold promise for a wide range of diseases. In contrast, the virus-like particle (VLP) vaccine platform can only be used in certain virus diseases, such as HBV and HPV.

  8. Stability: CGV is stable (resistant to 7 atmospheres) at room temperature for one month and at 4 C for one year.

  9. Cost-effective production: Manufacturing CGVs in E. coli offers a cost-effective approach for large-scale production. CGVs are expressed and purified from E. coli directly without further processes of conjugation, assembly, and adjuvant addition.

  10. Streamlined Development: CGV vaccines may benefit from a shorter R&D timeline compared to other subunit vaccine platforms.