Coronavirus vaccine formulations

Inventors

Smith, Gale • MASSARE, Michael J. • Tian, Jing-Hui

Assignees

Novavax Inc

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 relates to non-naturally occurring coronavirus Spike (CoV S) glycoprotein antigens engineered to alter SARS-CoV-2 Spike properties. A non-naturally occurring SARS-CoV-2 CoV S glycoprotein is described with an inactivated furin cleavage site by mutation of amino acids 669-672 to QQAQ (SEQ ID NO: 7), compared to a native CoV S glycoprotein. The antigen further includes mutation of amino acids 973 and 974 to proline, with amino acids numbered according to SEQ ID NO: 2.

The engineered CoV S glycoprotein is also described with additional structural stabilizing mutations intended to maintain a prefusion-stabilized conformation. In the provided description, Lys/Val substitutions to proline are noted at positions K986P and V987P, and additional proline substitutions at K973P and V974P are referenced. Optional deletions are described as including fusion peptide deletion, N-terminal domain (NTD) deletion, and TMCT deletion (transmembrane and cytoplasmic domain deletion).

For antigen presentation and stability, the disclosure describes forming detergent-core nanoparticles in which spike trimers are assembled with a non-ionic detergent core (including PS80) to generate nanoparticles. The disclosure further describes characterization of nanoparticle properties and formation concepts including detergent extraction/detergent exchange and lentil lectin affinity concepts. The engineered spike antigens are used within immunogenic compositions formulated with saponin-based adjuvants and a pharmaceutically acceptable buffer, with examples including ISCOM and ISCOM matrix (including MATRIX-M™ and Quillaja fractions).

Claims Coverage

The partial claim set contains one independent claim. This independent claim includes three inventive elements: a specifically modified non-naturally occurring SARS-CoV-2 CoV S glycoprotein (two modifications), a saponin adjuvant, and a pharmaceutically acceptable buffer.

Across the independent claim, the coverage is centered on a saponin-adjuvanted immunogenic composition using a non-naturally occurring SARS-CoV-2 CoV S glycoprotein with an inactivated furin cleavage site (QQAQ at 669-672) and proline substitutions (973-974), formulated in a pharmaceutically acceptable buffer.

Stated Advantages

Documented Applications