Thermostable vaccines based on ether lipids and native viral envelope proteins

Inventors

Foster, David • Emco Havenga, Menzo Jans

Assignees

Batavia Biosciences Inc

Abstract

A platform enabling the manufacture of thermostable vaccines by incorporating recombinantly expressed, viral envelope proteins in their native conformation into ether glycerophospholipid nanodisc structures that simulate the natural environment of the envelope proteins. The ether glycerophospholipids include ether-linked hydrophobic side chains, and are derived from or modeled after those found in thermophile bacteria, which increase thermostability, thereby significantly enhancing the vaccine's potency, enabling the production of highly multivalent vaccines incorporating multiple variants of the viral antigen, and improving stability and shelf-life.

Core Innovation

The invention provides a thermostable vaccine carrier comprising a bilayer with one or more ether glycerophospholipids and one or more membrane scaffold proteins self-assembled into a nanodisc, with a microbial protein antigen embedded in the nanodisc. The microbial protein antigen is described as a viral envelope protein antigen in native, substantially non-denatured conformation. The platform is presented as a carrier that maintains antigen integrity while forming a nanodisc structure based on membrane scaffold proteins.

The carrier uses ether linkages in the ether glycerophospholipids, with the description modeling the ether lipid chemistry on archaeal and thermophilic lipid structures such as phytanyl ether lipids and glycerol dialkyl glycerol tetraether variants. The ether linkage approach is described as increasing nanodisc thermostability and shelf-life. The thermostable nanodisc platform is further described as enhancing vaccine potency and enabling highly multivalent formulations.

The description further provides compositions and related vaccination kit components for use with the thermostable vaccine carrier. Example antigen targets include Influenza hemagglutinin, Ebola VP40/GP, and Zika envelope protein, and the scope is expressed for DNA viruses and RNA viruses by specifying viral envelope proteins. The nanodisc assembly and loading are described in terms of detergent solubilization followed by detergent removal to preserve protein conformation, with supporting characterization described in terms such as size, geometry, and thermostability comparisons.

Claims Coverage

The independent claim covers one core combination: a thermostable vaccine carrier that includes an ether-glycerophospholipid nanodisc self-assembled from membrane scaffold proteins with a microbial protein antigen embedded. Dependent claims refine the ether glycerophospholipid selection, specify membrane scaffold protein sequences or variants, narrow the microbial antigen to virus envelope proteins with DNA and RNA virus subcategories, and add formulation and kit limitations. Across the claim family, the inventive features number at least four main aspects.

The discussed claim set centers on an ether-glycerophospholipid-based nanodisc vaccine carrier with membrane scaffold proteins and an embedded microbial protein antigen, further constrained by enumerated ether glycerophospholipid options, specific scaffold protein sequence selection, and narrowing of the antigen to viral envelope proteins from RNA viruses.

Stated Advantages

Documented Applications