University System of Maryland

National Research Council of Canada

James Eugene Galen

Myron M Levine

Hanping Feng

Wangxue Chen

Raphael Simon

Sharon Tennant

Christofer Vindurampulle

Kevin Chen

Jin-Yuan Wang

Yixuan Zhu

Dacie R Bridge

Thanh Pham

Jin Yuan Wang

Eileen M Barry

Chee-Mun Fang

Yuansha Chen

The present invention provides compositions and methods of inducing an immune response in a subject in need thereof, comprising administering to the subject an immunologically-effective amount of a livevector comprising a heterologous antigen from a pathogen, wherein the heterologous antigen comprises an outer membrane protein, an antigenic fragment thereof or a variant thereof, wherein the antigen is delivered to a mucosal tissue of the subject by an outer membrane vesicle.

Livetyphi vectors engineered to express heterologous outer membrane protein antigens and methods of use thereof

Antibody-based binding agents derived from human and camelid immunoglobulins are described, as well as strains of yeast engineered to secrete the binding agents, and methods of treating and preventinginfections using the engineered strains of yeast. These binding agents recognize and bind with specificity totoxin A and/or toxin B and in some cases exhibit toxin neutralizing activity. The binding agents include camelid VH peptide monomers, linked groups of VH peptide monomers, VH peptide monomers joined to antibody Fc domains, and VH peptide monomers joined to IgG antibodies.

Yeast-based immunotherapy againstinfection

The present invention provides compositions and methods of inducing an immune response in a subject in need thereof, comprising administering to the subject an immunologically-effective amount of a liveTyphi vector comprising a heterologous antigen from a pathogen, wherein the heterologous antigen comprises an outer membrane protein, an antigenic fragment thereof or a variant thereof, wherein the antigen is delivered to a mucosal tissue of the subject by an outer membrane vesicle.

Livevectors engineered to express heterologous outer membrane protein antigens and methods of use thereof

Yeast-based immunotherapy against clostridium difficile infection

The invention relates to a multivalentvaccine comprising alive vector comprising the cell binding domain of TcdA toxin (CBD/A) ofor an antigenic fragment thereof and the cell binding domain of TcdB toxin (CBD/B) ofor an antigenic fragment thereof and optionally the cell-binding subunit component (CdtB) of binary toxin ofor an antigenic fragment thereof. The invention further provides methods of inducing an immune response and methods of preventing recurrence ofinfections in subjects.

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Bacterial live vector vaccines represent a vaccine development strategy that offers exceptional flexibility. In the present invention, genes encoding protective antigens of unrelated bacterial, viral, parasitic, or fungal pathogens are expressed in an attenuated bacterial vaccine strain that delivers these foreign antigens to the immune system, thereby eliciting relevant immune responses. Rather than expressing these antigens using only low copy expression plasmids, expression of foreign proteins is accomplished using both low copy expression plasmids in conjunction with chromosomal integrations within the same live vector. This strategy compensates for the inherent disadvantage of loss of gene dosage (versus exclusive plasmid-based expression) by integrating antigen expression cassettes into multiple chromosomal sites already inactivated in an attenuated vector.

Bacterial live vector vaccines expressing chromosomally-integrated foreign antigens

The disclosure below provides a protein export system utilizing non-hemolytic variants of HlyE family member proteins for efficiently producing recombinant protein from a host cell. In a preferred embodiment, the protein export system utilizes protein export machinery endogenous to the host bacterium into which the protein export system vector is introduced.

Non-hemolytic ClyA for excretion of proteins

The present invention is drawn to attenuatedserovar strainsand, conjugate vaccines derived from these attenuated strains ofand, comprising an O polysaccharide covalently linked to a flagellin protein, and methods for inducing an immune response in a subject comprising administering the attenuated strains and/or the conjugate vaccines of the invention.

The present invention is drawn to multivalentserovar conjugate vaccines comprising conjugates ofA and optionallyB, wherein the conjugates comprise a hapten antigen and a carrier antigen, wherein at least one of the hapten antigens or carrier antigens is characteristic of theserovar. The present invention also providesserovar reagent strains to produce the multivalent conjugate vaccines and attenuatedserovars for use as vaccines.

The present invention relates generally to stabilized expression plasmid systems. The stabilized expression plasmid systems comprise an expression vector that includes a plasmid maintenance system (PMS) and, optionally, one or both of a polynucleotide encoding a selected antigen under control of a promoter, and a polynucleotide encoding a selectable marker under control of a promoter. The use of the mchI protein as a selectable marker is found in preferred embodiments of the invention.

Microcin H47 plasmid selection system

The present invention is drawn to a live, attenuatedA strain, a live, attenuatedA strain comprising a stabilized plasmid expression system, anconjugate vaccine, and methods of using these strains and conjugate vaccine.

The present invention relates generally to a Plasmid Maintenance System for the stabilization of expression plasmids encoding foreign antigens, and methods for making and using the Plasmid Maintenance System. The invention optimizes the maintenance of expression plasmids at two independent levels by: (1) removing sole dependence on balanced lethal maintenance functions; and (2) incorporating at least one plasmid partition function to prevent random segregation of expression plasmids, thereby enhancing their inheritance and stability. The Plasmid Maintenance System may be employed within a plasmid which has been recombinantly engineered to express a variety of expression products.

Plasmid maintenance system for antigen delivery

The disclosure below provides a protein export system for efficiently producing recombinant protein from a host cell. In a preferred embodiment, the protein export system utilizes protein export machinery endogenous to the host bacterium into which the protein export system vector is introduced.

Growing community of inventors

Sykesville, MD, United States of America

James Eugene Galen