Vaccine compositions having improved stability and immunogenicity
Inventors
Smith, Gale • Liu, Ye • Tian, Jing-Hui • MASSARE, Michael J. • BODDAPATI, Sarathi • Shane, Erica • Oliver, Cynthia • Glenn, Gregory
Assignees
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Publication Number
US-12257297-B2
Publication Date
2025-03-25
Expiration Date
Abstract
Disclosed herein are nanoparticles suitable for use in vaccines. The nanoparticles present antigens from pathogens surrounded to and associated with a detergent core resulting in enhanced stability and good immunogenicity. Dosages, formulations, and methods for preparing the vaccines and nanoparticles are also disclosed.
Core Innovation
The invention provides vaccine compositions in the form of nanoparticles that include a pathogen antigen arranged around a non-ionic detergent core. In particular, an Ebola virus glycoprotein (GP) nanoparticle is described, where the GP comprises a GP1 domain and a GP2 domain that are connected via a disulfide bond, and the GP2 polypeptide is associated with the non-ionic detergent core while the GP1 polypeptide extends outward. The GP is a trimer.
The disclosed nanoparticle architecture is positioned as a solution for enhanced epitope presentation and improved stability of the antigen. The platform is aimed at addressing antigen instability and maintaining antigenic integrity under stressed conditions while preserving immunogenicity. The platform uses detergent-core-associated antigen trimers to maintain antigenic site integrity and to support epitope presentation.
A detergent-core-associated manufacturing approach is described that includes detergent extraction and detergent exchange around the recombinant antigen. The material also describes representative non-ionic detergents for the detergent core, including PS20, PS40, PS60, PS65, and PS80, and notes that the approach can be used in conjunction with formulation components in pharmaceutically acceptable buffers. Optional adjuvants are described, including alum (AlPO4) and Matrix-M / ISCOM saponin fractions A and C.
Claims Coverage
The identified independent claim provides composition coverage for an Ebola virus GP-containing nanoparticle formed by association of a GP trimer with a non-ionic detergent core, with a specific GP1/GP2 disulfide linkage and domain orientation. The remaining dependent claims refine this core composition toward specific GP identity, detergent selection, immunogenic formulations including saponin adjuvants, and insect-cell expression context.
Ebola virus glycoprotein nanoparticle with non-ionic detergent core
A nanoparticle comprising an Ebola virus glycoprotein (GP) and a non-ionic detergent core, wherein the GP comprises a GP1 domain and a GP2 domain, wherein the GP1 domain and GP2 domain are connected via a disulfide bond, wherein the GP2 polypeptide is associated with the non-ionic detergent core and the GP1 polypeptide extends outward, and wherein the GP is a trimer.
The claim coverage centers on a nanoparticle composition where an Ebola virus GP trimer has a disulfide-connected GP1 and GP2, with GP2 associated with a non-ionic detergent core and GP1 extending outward to support epitope presentation. Dependent claim refinements further restrict GP identity and select specific non-ionic detergents, and define related immunogenic compositions that include the nanoparticle with a saponin adjuvant in a pharmaceutically acceptable buffer, along with additional narrowing to particular adjuvant fractions and insect-cell expression context.
Stated Advantages
Enhanced stability, including improved forced-degradation/thermostability.
Maintained antigenic site integrity and preserved immunogenicity across stressed samples.
Protease resistance.
Improved epitope presentation.
Documented Applications
Vaccine compositions using Ebola GP nanoparticle vaccines, with described protective efficacy for Ebola GP nanoparticle vaccines with saponin adjuvant.
Vaccine compositions using influenza and RSV nanoparticle vaccines, with described improved folding/stability.
Use of the disclosed nanoparticle platform in animal model studies including mice, baboons, and macaques, with reported enhanced antibody titers, T-cell responses, and protective efficacy for Ebola GP.
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