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-10058608-B2
Publication Date
2018-08-28
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 low-cost, liquid vaccine and adjuvant compositions for inducing antibodies against FimH in a human. The compositions use an antigen of FimCH or truncated FimH, combined with an adjuvant formulation that contains about 20 micrograms to about 50 micrograms of one or more specified compounds or pharmaceutically acceptable salts thereof.
The adjuvant formulation is a synthetic TLR4 agonist, including phosphorylated hexaacyl disaccharide and 3-deacyl-phosphorylated hexaacyl disaccharide and PtHA variants. The compositions are aqueous buffered suspensions, with buffered components such as citrate, succinate, and phosphate, and formulation pH ranges and stability-oriented suspension characteristics.
The disclosure additionally includes vaccine composition embodiments that include phosphatidylcholine, with example embodiments specifying aqueous buffered suspension conditions having a defined pH range and mean particle size limits. The compositions are stable under refrigerated conditions and during storage and shipping exposure up to elevated temperatures without lyophilization, while reducing severe injection-site/systemic reactions compared to prior adjuvants.
Claims Coverage
The partial content provides four independent claims. Across these independent claims, the inventive coverage centers on inducing production of antibodies against FimH in a human using a vaccine composition that combines a FimCH or truncated FimH antigen with a TLR4 agonist adjuvant formulation dosed at about 20 micrograms to about 50 micrograms of specified compounds or salts.
Inducing antibodies against FimH with FimCH or truncated FimH plus a specified microgram-dose adjuvant
A method of inducing the production of antibodies against FimH in a human by administering a vaccine composition comprising an effective amount of an antigen of FimCH or truncated FimH, and an adjuvant formulation containing about 20 micrograms to about 50 micrograms of one or more of specified compounds, or pharmaceutically acceptable salts thereof.
FimCH or truncated FimH vaccine composition with about 20–50 microgram-dose specified adjuvant
A vaccine composition comprising an effective amount of an antigen of FimCH or truncated FimH, and an adjuvant formulation containing about 20 micrograms to about 50 micrograms of one or more of specified compounds, or mixtures thereof, or pharmaceutically acceptable salts thereof.
The independent-claim core in the partial content is directed to antibody induction against FimH in a human using a vaccine composition that pairs a FimCH or truncated FimH antigen with a specified adjuvant formulation at about 20 micrograms to about 50 micrograms of the listed adjuvant compounds or pharmaceutically acceptable salts.
Stated Advantages
Improved stability of PHAD formulations when formulated with citrate, succinate, or phosphate buffers.
Controlled formulation characteristics, including mean particle size control to less than 150 nm with extrusion and formulation characterization by particle size and zeta potential.
Antibody responses against FimH are described comparatively, with evidence that formulation parameters affect immunogenicity.
The patent includes evidence for human interim safety/reactogenicity and immunogenicity, and supporting toxicity and mouse efficacy data.
Exceptional stability at refrigerated conditions and during storage and shipping exposure up to about 37°C for extended periods without lyophilization.
Reduction of severe injection-site/systemic reactions compared with prior adjuvants, including MF59, MPL, and alum.
Documented Applications
Vaccine compositions and methods for inducing the production of antibodies against FimH in a human, including prevention and/or treatment of urinary tract infections caused by gram-negative bacteria and drug-resistant Escherichia coli.
Inducing anti-FimH antibodies in humans with recurrent urinary tract infections.
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