Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8821893-B2
Publication Date
2014-09-02
Expiration Date
Abstract
The present invention relates to vaccines for control of Borrelia infections in animal and human populations. In particular, the present invention provides compositions and methods comprising recombinant bacteria engineered to express one or more Borrelia burgdorferi antigens for use as Lyme disease vaccines. In some embodiments, the recombinant bacteria are freeze-dried.
Core Innovation
The invention relates to an oral Lyme disease vaccination approach using a lyophilized Escherichia coli and a Lactobacillus plantarum bacterium engineered to express a protein comprising a modified amino acid sequence set forth herein as SEQ ID NO:2. The modified SEQ ID NO:2 comprises a deletion of the hLFA1 epitope SEQ ID NO:5 (YVLEGTLTA), and is used to elicit an antibody response against a Borrelia burgdorferi outer surface protein.
The approach centers on formulating the engineered, freeze-dried bacteria as an oral vaccine composition and administering it under conditions suitable for eliciting antibodies against a Borrelia burgdorferi outer surface protein. The Borrelia burgdorferi outer surface proteins described include outer surface protein targets notably OspA and OspC, including OspA with a hLFA1-mutated or deleted epitope and selected OspC types or chimeras.
The disclosed concepts include use of food carriers or excipients for the oral delivery of the lyophilized engineered bacteria, including dairy products and grain products, together with excipient categories such as sugars, starches, gums, and proteins. The disclosure also describes assessment frameworks across lab mice and wildlife, and includes planned human clinical trials with antibody titer measurements and effectiveness metrics, with proof-of-concept results indicating systemic IgG responses and protection after oral administration.
Claims Coverage
The independent claim recites an oral immunizing method that combines a specific lyophilized engineered Escherichia coli and Lactobacillus plantarum vaccine composition expressing modified SEQ ID NO:2 with deletion of the hLFA1 epitope and oral administration to elicit antibodies against a Borrelia burgdorferi outer surface protein. Dependent claims add several refinements, including quantitative, formulation, subject, and administration limitations, resulting in multiple inventive features.
Lyophilized oral bacteria engineered for modified SEQ ID NO:2 with hLFA1 epitope deletion
An oral vaccine composition comprising a lyophilized Escherichia coli and Lactobacillus plantarum bacterium engineered to express a protein comprising modified amino acid sequence SEQ ID NO:2, wherein the modified SEQ ID NO:2 comprises a deletion of the hLFA1 epitope SEQ ID NO:5 (YVLEGTLTA).
Oral administration to elicit antibodies against Borrelia burgdorferi outer surface protein
Orally administering the oral vaccine composition to a subject under conditions suitable for eliciting an antibody response against a Borrelia burgdorferi outer surface protein.
Serum IgG titer threshold against outer surface protein
The antibody response is characterized by an outer surface protein-reactive serum IgG titer of at least 1:100.
More than one meal oral administration
Orally administering the treatment using more than one meal.
Enumerated Lactobacillus species selection
The bacterium is a Lactobacillus selected from the listed species including L. plantarum and others in the enumerated set.
Feral mammal subject selection
Applied to a feral mammal including one or more specified animal types such as mouse, chipmunk, squirrel, shrew, vole, rat, raccoon, opossum, skunk, rabbit, and deer.
Dairy or grain food carrier selection
The food carrier includes either a selected dairy product (milk, yogurt, or cheese) or a selected grain product (grain, seed, bread, and cereal).
The claim coverage centers on the lyophilized oral vaccine composition using engineered Escherichia coli and Lactobacillus plantarum expressing modified SEQ ID NO:2 with deletion of the hLFA1 epitope, together with oral administration to elicit antibodies against Borrelia burgdorferi outer surface proteins. Additional claim features narrow the scope by specifying serum IgG titer, multi-meal administration, Lactobacillus selection, food carrier categories, and feral mammal subject selection.
Stated Advantages
Elicits systemic antibody responses, including outer surface protein-reactive serum IgG responses, following oral administration.
Provides protection against B. burgdorferi challenge.
Documented Applications
Oral vaccination approach for Lyme disease using lyophilized, engineered recombinant bacteria to elicit antibody responses against Borrelia burgdorferi outer surface proteins and assess protection metrics.
Assessment in lab mice and wildlife, including measurement of antibody titers and protection/effectiveness metrics following challenge.
Planned human clinical trials with efficacy metrics based on antibody responses such as IgG and mucosal IgA titers.
Interested in licensing this patent?