West nile virus vaccine and method of use thereof
Inventors
Clements, David E. • Van Hoeven, Neal
Assignees
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Publication Number
US-11135281-B2
Publication Date
2021-10-05
Expiration Date
Abstract
A West Nile virus (WNV) vaccine for human use is described that contains a recombinantly produced form of truncated WNV envelope glycoprotein and a combination of a Toll-like receptor 4 (TLR-4) and saponin adjuvants. A pharmaceutically acceptable vehicle may also be included in the vaccine.
Core Innovation
The invention provides a human vaccine comprising purified West Nile virus (WNV) envelope E polypeptide and adjuvants. The E polypeptide is truncated such that it constitutes approximately 80% of the length of wild type E starting from amino acid residue 1 at its N-terminus, and the vaccine induces the production of neutralizing antibodies in human subjects.
The vaccine includes an effective amount of a Toll-like receptor 4 (TLR-4) agonist and an effective amount of a purified saponin adjuvant. The TLR-4 agonist and the saponin are combined to form a liposome formulation, and in particular embodiments the TLR-4 agonist is synthetic lipid A (SLA) and the saponin adjuvant is QS21.
The document also describes the truncated, properly folded WN-80E envelope E subunit combined with a TLR-4 agonist and a saponin adjuvant to generate strong, durable neutralizing antibody responses in humans. It further states acceptable safety in healthy and immunocompromised individuals, including use in immunodeficient subjects, and experimental support showing immune responses and neutralization.
Claims Coverage
The partial content includes two independent claims. The independent claims cover a WNV envelope E subunit vaccine for human use with neutralizing antibody induction, with claim coverage centered on the truncated E polypeptide, the TLR-4 agonist and purified saponin adjuvant, and the liposome formulation; one claim also specifies SLA plus QS21 as LSQ.
Truncated purified WNV envelope E polypeptide as approximately 80 percent from N-terminal residue 1
An effective amount of purified West Nile virus envelope E polypeptide, wherein the E polypeptide constitutes approximately 80% of the length of wild type E starting from amino acid residue 1 at its N-terminus.
TLR-4 agonist and purified saponin adjuvant combined into a liposome formulation
An effective amount of a Toll-like receptor 4 (TLR-4) agonist and an effective amount of a purified saponin adjuvant, wherein the TLR-4 agonist and the saponin are combined to form a liposome formulation.
Neutralizing antibody induction in human subjects
The vaccine induces the production of neutralizing antibodies in human subjects.
Purified protein of SEQ ID NO: 2 as the vaccine protein component
An effective amount of purified protein of SEQ ID NO: 2.
Synthetic lipid A and QS21 combined to form LSQ liposome formulation
An effective amount of a synthetic lipid A (SLA) adjuvant and an effective amount of the purified saponin QS21 adjuvant, wherein the SLA and QS21 adjuvant are combined to form a liposome formulation (LSQ).
The independent claims collectively cover a vaccine formulation for human subjects that pairs a truncated WNV envelope E subunit with a TLR-4 agonist and a purified saponin adjuvant. The claims require the TLR-4 agonist and the saponin to be combined into a liposome formulation and require induction of neutralizing antibodies in human subjects; one claim additionally specifies SLA plus QS21 as LSQ.
Stated Advantages
Induces the production of neutralizing antibodies in human subjects.
Expected acceptable safety in healthy and immunocompromised individuals.
Documented Applications
A Phase 1 clinical trial is referenced for the vaccine in humans, including use in healthy and immunocompromised individuals.
Preclinical immune and challenge evaluation is described using mouse and Syrian hamster challenge models.
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