West nile virus vaccine comprising WN-80E recombinant subunit protein
Inventors
Coller, Beth-Ann • Pai, Vidya • Weeks-Levy, Carolyn L. • Ogata, Steven A.
Assignees
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Publication Number
US-10039820-B2
Publication Date
2018-08-07
Expiration Date
Abstract
A West Nile virus vaccine for human use is described that preferably contains a recombinantly produced form of truncated West Nile virus envelope glycoprotein and aluminum adjuvant. The vaccine is acceptable for use in the general population, including immunosuppressed, immunocompromised, and immunosenescent individuals. The vaccine is safe and effective for use in all healthy and at-risk populations. A pharmaceutically acceptable vehicle may also be included in the vaccine.
Core Innovation
The invention is directed to a human West Nile virus vaccine that comprises an effective amount of a purified protein as set forth in SEQ ID NO:1 together with an effective amount of aluminum hydroxide adjuvant, formulated in a dosage form of 15–50 ug per dose. The vaccine induces the production of neutralizing antibodies for West Nile virus in human subjects.
The purified protein of SEQ ID NO:1 is described as a recombinant truncated E glycoprotein subunit (WN-80E, ~80%/aa 1–401) with C-terminal truncation that allows secretion. The recombinant protein is produced in Drosophila S2 cells, and the vaccine is formulated with an aluminum hydroxide (alum) adjuvant.
The description positions the vaccine as achieving neutralizing antibodies with an acceptable safety profile, including in healthy and at-risk populations such as immunocompromised/immunosenescent subjects. It is further asserted that protection/immunogenicity is achieved without inclusion of NS1, and that the protein remains suitable for binding to and adsorption by the aluminum hydroxide adjuvant.
Documented formulation and characterization include an alum binding/adsorption requirement, for example at least 75% adsorption, and support for cGMP manufacture. Phase 1 findings described include tolerability characterized by mostly mild injection-site reactions and neutralizing antibody titers with a reported threshold response for the alum-formulated vaccine.
Claims Coverage
The independent claim covers a vaccine composition containing a purified protein defined by SEQ ID NO:1 and an aluminum hydroxide adjuvant, formulated at 15–50 ug per dose, where the vaccine induces neutralizing antibodies against West Nile virus in human subjects. The claim set adds four related inventive features.
Purified protein of SEQ ID NO:1 plus aluminum hydroxide adjuvant in a 15–50 ug per dose vaccine
A vaccine comprising an effective amount of purified protein as set forth in SEQ ID NO:1 and an effective amount of aluminum hydroxide adjuvant, formulated in dosage form of 15–50 ug per dose, wherein the vaccine induces the production of neutralizing antibodies for West Nile virus in human subjects.
Recombinant production of the E polypeptide in insect host cells
The vaccine includes the E polypeptide that is recombinantly produced and expressed in insect host cells.
Adsorption of at least 75% of the protein of SEQ ID NO:1 to the adjuvant
The vaccine is characterized by having at least 75% of the protein of SEQ ID NO:1 adsorbed to the adjuvant.
Use for immunodeficient subjects
The vaccine is for use in subjects with immunodeficiencies rather than healthy subjects.
Across the claim set, the inventive concept is a SEQ ID NO:1 purified protein vaccine formulated with aluminum hydroxide to induce West Nile virus neutralizing antibodies in humans, with refinements that specify recombinant insect-cell expression, a defined adsorption level to the adjuvant, and an intended use for immunodeficient subjects.
Stated Advantages
Induces the production of neutralizing antibodies for West Nile virus in human subjects.
Achieves an acceptable safety profile, including mostly mild injection-site reactions described in Phase 1.
Protection/immunogenicity is asserted to be achieved without inclusion of NS1.
Neutralizing antibody responses are described with PRNT50 thresholds and responders reported for the alum-formulated vaccine.
Documented Applications
A vaccine for producing West Nile virus neutralizing antibodies in human subjects.
Use in subjects with immunodeficiencies, including immunocompromised/immunosenescent populations described in the provided content.
Clinical evaluation in a Phase 1 setting, with tolerability and neutralizing antibody outcomes reported.
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