Production of flu vaccine in Myceliophthora thermophila
Inventors
EMALFARB, Mark • Verwoerd, Teunis Cornelis • Alfenito, Mark R. • Baer, Mark • Legastelois, Isabelle • KAZEK, Marie-Pierre • BERNARD, Marie-Clotilde • Dubayle, Jean • KENSINGER, Richard
Assignees
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Publication Number
US-11738080-B2
Publication Date
2023-08-29
Expiration Date
Abstract
Recombinant expression of influenza virus surface proteins in the fungus Myceliophthora thermophila strain C1 is provided. The recombinant proteins are for use in influenza vaccine compositions.
Core Innovation
The invention genetically modifies Myceliophthora thermophila C1 to produce an influenza virus surface protein by using an expression construct. The expression construct comprises a nucleic acid sequence encoding the influenza virus surface protein operably linked to at least one C1 regulatory sequence, and the protein comprises its ectodomain and transmembrane domain as a membrane-bound protein.
The disclosed approach uses C1 regulatory sequences to drive expression of membrane-bound influenza virus surface proteins, including C1 regulatory sequences such as hex1/chi1/cbh1 promoters and C1 signal peptides. Functional constructs include the transmembrane domain, while non-functional secreted or truncated constructs are contrasted with HA constructs that lack the functional TMD arrangement.
As reported, expressing the influenza virus surface protein as an ectodomain plus transmembrane domain membrane-bound protein supports functional, dose-dependent immune responses in mice, including hemagglutination inhibition titers. The document further describes use of the produced virus surface proteins in vaccine compositions, including formulations without added adjuvant.
Claims Coverage
The partial claims content identifies 1 independent claim. The independent claim centers on a genetically-modified Myceliophthora thermophila C1 engineered for membrane-bound expression of an influenza virus surface protein that includes both ectodomain and transmembrane domain under control of C1 regulatory sequences.
C1 membrane-bound influenza surface protein expression with ectodomain and transmembrane domain under C1 regulatory sequences
A genetically-modified Myceliophthora thermophila C1 comprising an expression construct in which a nucleic acid sequence encoding an influenza virus surface protein is operably linked to at least one C1 regulatory sequence, wherein the influenza virus surface protein comprises its ectodomain and transmembrane domain and is expressed in the C1 as a membrane-bound protein.
The claim coverage focuses on configuring C1 regulatory elements so that an influenza virus surface protein is expressed in Myceliophthora thermophila C1 as a membrane-bound protein containing its ectodomain and transmembrane domain.
Stated Advantages
Functional, dose-dependent immune responses in mice, including hemagglutination inhibition titers.
Documented Applications
Vaccine compositions comprising the produced influenza virus surface protein, including formulations without added adjuvant.
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