Compositions of vaccines and adjuvants and methods for the treatment of urinary tract infections
Inventors
Eldridge, Gary • Martin, Steven M
Assignees
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Publication Number
US-10525128-B2
Publication Date
2020-01-07
Expiration Date
Abstract
This invention describes novel adjuvant compositions and formulations with excellent stability at refrigerated and room temperatures and up to and about 37° C. that can be produced at remarkably low costs. This invention describes novel vaccine compositions and formulations to treat and prevent urinary tract infections caused by gram-negative bacteria including Escherichia coli and multi-drug resistant E. coli. This invention also describes methods of administration of said novel vaccine compositions and formulations and methods of treatment to prevent and treat urinary tract infections caused by gram-negative bacteria including E. coli and multi-drug resistant E. coli.
Core Innovation
The invention relates to vaccine adjuvant and vaccine formulations based on synthetic phosphorylated hexaacyl disaccharide (PHAD) and derivative 3-deacyl-phosphorylated hexaacyl disaccharide, including penta-to-hexaacyl diglucosamine (PtHA) adjuvants. The vaccine composition includes an antigen of FimCH or truncated FimH together with an adjuvant and an aqueous buffered suspension, characterized by a mean particle size of 150 nanometers or less.
The formulations are essentially free of metabolizable oil used as an adjuvant and are not oil-in-water emulsion, including being essentially free of metabolizable oils such as squalene. FimCH is described as non-covalent FimC+FimH, and truncated FimH is described as FimHt.
The disclosure further connects these PHAD/PtHA-based formulations to inducing antibodies against FimH in humans with recurrent urinary tract infections. The document also states that the PHAD-based buffered suspensions provide exceptional stability, including stability from refrigerated conditions to up to about 37°C without lyophilization.
Claims Coverage
The document provides two independent claims: one method claim and one vaccine composition claim. Across these independent claims, the coverage includes the FimCH or truncated FimH antigen, an adjuvant, an aqueous buffered suspension with mean particle size of 150 nanometers or less, and the exclusion of metabolizable oil used as an adjuvant and of oil-in-water emulsion.
Human antibody induction for recurrent urinary tract infections
A method of inducing the production of antibodies against FimH in a human with recurrent urinary tract infections by administering a vaccine composition comprising an antigen of FimCH or truncated FimH, an adjuvant, and an aqueous buffered suspension.
Aqueous buffered suspension with mean particle size of 150 nanometers or less
The vaccine composition includes an aqueous buffered suspension that has a mean particle size of 150 nanometers or less.
No metabolizable oil and not an oil-in-water emulsion
The vaccine composition is essentially free of metabolizable oil used as an adjuvant and is not an oil-in-water emulsion.
Vaccine composition including FimCH or truncated FimH
A vaccine composition comprising an antigen of FimCH or truncated FimH, an adjuvant, and an aqueous buffered suspension that has a mean particle size of 150 nanometers or less.
Overall claim coverage emphasizes antibody induction against FimH using a FimCH or truncated FimH antigen combined with an adjuvant in an aqueous buffered suspension defined by mean particle size at or below 150 nanometers and by being essentially free of metabolizable oil used as an adjuvant, such that the composition is not an oil-in-water emulsion.
Stated Advantages
Exceptional stability, including stability from refrigerated conditions to up to about 37°C without lyophilization.
Reduced injection site and systemic reactions.
Lower-cost manufacturing.
Potential for sterile ready-to-fill syringe packaging.
Enables inducing production of antibodies against FimH in a human with recurrent urinary tract infections.
Avoids using metabolizable oil as an adjuvant and is not an oil-in-water emulsion.
Documented Applications
Vaccine concepts for Gram-negative bacteria, including prevention and treatment of recurrent urinary tract infections associated with E. coli and multidrug-resistant E. coli, using FimCH or truncated FimH antigens to induce anti-FimH antibodies in humans.
Vaccine preparations incorporating PtHA adjuvants into FimCH/truncated FimH vaccine preparations targeting E. coli and multidrug-resistant E. coli.
Administration of an adjuvanted FimCH/PHAD formulation for recurrent urinary tract infection context, including mouse UTI CFU reduction and immunogenicity/toxicity evaluations in rabbit GLP studies.
Human use context, including early clinical safety and interim antibody response observations.
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