Coronavirus vaccine formulations
Inventors
Smith, Gale • MASSARE, Michael J. • Tian, Jing-Hui
Assignees
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Publication Number
US-11541112-B2
Publication Date
2023-01-03
Expiration Date
Abstract
Disclosed herein are coronavirus Spike (S) proteins and nanoparticles comprising the same, which are 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 disclosure describes an immunogenic composition that includes a nanoparticle comprising a coronavirus S (CoV S) glycoprotein and a non-ionic detergent core. The CoV S glycoprotein contains a sequence that is at least 95% identical to SEQ ID NO: 2, and includes amino acids 669-672 as QQAQ (SEQ ID NO: 7) and amino acids 973 and 974 as proline, with numbering relative to SEQ ID NO: 2.
The nanoparticles are associated with a non-ionic detergent core using detergent-associated approaches, including polysorbates such as PS20, PS40, PS60, PS65, and PS80. The disclosure states that the detergent core enhances antigen stability, size homogeneity, and thermal robustness, and may improve epitope presentation and hACE2 binding under stress conditions.
The composition further includes a pharmaceutically acceptable buffer and a saponin adjuvant, including saponin-based ISCOM or ISCOM matrix formulations. Quillaja saponaria Molina saponin fractions are described as being used within ISCOM/ISCOM matrix adjuvants, including MATRIX-M™ with Fraction A and Fraction C.
Claims Coverage
The provided independent claim recites an immunogenic composition defined by two inventive features: a detergent-core nanoparticle presenting a coronavirus S glycoprotein with defined substitutions, and formulation with a pharmaceutically acceptable buffer and a saponin adjuvant. Dependent claims further constrain the detergent selection, the saponin/ISCOM composition, and dosing/schedule parameters.
Detergent-core nanoparticle with engineered CoV S glycoprotein substitutions
A nanoparticle comprising a coronavirus S (CoV S) glycoprotein and a non-ionic detergent core, wherein the glycoprotein comprises a sequence that is at least 95% identical to SEQ ID NO: 2; and wherein amino acids 669-672 are QQAQ (SEQ ID NO: 7) and amino acids 973 and 974 are proline, numbered with respect to SEQ ID NO: 2.
Saponin-adjuvanted immunogenic composition with buffer
A pharmaceutically acceptable buffer, and a saponin adjuvant, in an immunogenic composition comprising the nanoparticle.
Overall claim coverage is directed to an immunogenic composition built around a detergent-core nanoparticle that presents an engineered coronavirus Spike glycoprotein with defined furin-related and prefusion-stabilizing substitutions, and that is formulated with a pharmaceutically acceptable buffer and a saponin adjuvant. Dependent elements further constrain the non-ionic detergent choice to specific polysorbates and define the saponin adjuvant using ISCOM particles derived from Quillaja saponaria Molina fractions A and C.
Stated Advantages
Enhances antigen stability, size homogeneity, and thermal robustness.
May improve epitope presentation and hACE2 binding under stress.
Produces enhanced anti-Spike IgG responses.
Produces hACE2-blocking and virus neutralizing antibody responses.
Improves T-cell responses with Th1-skewed polyfunctional characteristics.
Reduced viral replication/loads in animal challenge models.
Favorable safety/tolerability.
Observed dose-sparing enabled by the saponin matrix adjuvant.
Documented Applications
Vaccine formulations that are administered to animals, including mice, olive baboons, and cynomolgus macaques, and in a Phase 1 human clinical trial, with reported immune responses and challenge-model outcomes.
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