The Administrators of the Tulane Educational Fund

Praxis Biologics, Inc.

Other

USA As Represented by Secretary of the Navy

Bergen Teknologioverføring

American Cyanamid Company

Bergen Teknologioverføring As

John D Clements

Bonny L Dickinson

Elizabeth Bray Norton

Robert F Garry

Charles Joel Arntzen

Hugh S Mason

Porter W Anderson

Bruce Alan Bunnell

Weiping Zhang

Suzanne L Tomchuck

Arne M Taxt

Pål Puntervoll

Haq A Tariq

Halvor Sommerfelt

James P Nataro

Sawsan E El-Morshidy

The invention provides compositions and methods for reducing symptoms of inflammation by administering therapeutically effective amounts of (a) (1) enterotoxicheat labile detoxified toxin A subunit that interferes with the function of ADP-ribosylation factor and inhibits ADP-ribosylation, or (2) A1 subunit that interferes with the function of ADP-ribosylation factor and inhibits ADP-ribosylation, or both (1) and (2), and (b) a carrier that causes internalization of the A subunit or A1 subunit, or both, into cells.

Mutated e. coli enterotoxins as anti-inflammatory agents

Episomally transfected primary mesenchymal stem cells (MSC) express a polypeptide consisting of an antigenic polypeptide (e.g., one or more polypeptides) relating to a pathogen (e.g., one or more virus, bacterium, or parasite). The antigenic polypeptide can have the amino acid sequence of a natural polypeptide from the pathogen or an amino acid sequence differing from the natural sequence by one or more conservative amino acid substitutions. Uses and method for treating or preventing infections with episomally transfected primary MSC also are described.

Primary mesenchymal stem cells as a vaccine platform

A mutant of anheat-stable toxin (ST) having the following wild-type sequence: NSSNYCCELCCNPACTGCY wherein the mutant comprises a mutation selected from the group consisting of: A14H, A14T and N12T.

Vaccine

The present invention provides a novel composition which is a hybrid heat labile enterotoxin comprising the A-subunit of the heat labile toxin of(LT-A) and the B-subunit of the cholera enterotoxin of(CT-B). The hybrid toxin is designated LT-A/CT-B. The LT-A subunit, the CT-B subunit, or both subunits of the hybrid toxin may be mutant subunits, e.g., differing from wild-type subunits by amino acid substitutions, deletions or additions. Also provided are methods of using the novel LT-A/CT-B comprising compositions of the invention as adjuvants for vaccines, methods of making the LT-A/CT-B hybrid holotoxin, and kits.

Hybrid LT-A/CT-B holotoxin for use as an adjuvant

Methods and compositions are provided herein for the se of a novel mutant form of heat-labile enterotoxin which has lost its toxicity but has retained its immunologic activity. This enterotoxin is used in combination with an unrelated antigen to achieve an increased immune response to said antigen when administered as part of an oral vaccine preparation.

Mutant enterotoxin effective as a non-toxic oral adjuvant

Methods and compositions are provided herein for the use of a novel mutant form of heat-labile enterotoxin which has lost its toxicity but has retained its immunologic activity. This enterotoxin is used in combination with an unrelated antigen to achieve an increased immune response to said antigen when administered as part of a vaccine preparation.

Mutant enterotoxin effective as a non-toxic adjuvant

Novel immunoregulatory utilities of heat-labile enterotoxin (LT) are disclosed. This enterotoxin can be used in combination with an unrelated antigen to achieve a higher immune response to said antigen when administered as part of an oral vaccine preparation. By way of example, the efficacy of oral adjuvant therapy of LT in the development of immunological protection against herpes simplex virus was examined. In addition, the ability of LT to influence the induction and maintenance of tolerance in animals primed orally with two unrelated protein antigens administered simultaneously, OVA and BSA was examined. Simultaneous administration of LT with OVA was shown to prevent the induction of tolerance to OVA and to increase the serum anti-OVA IgG response to 30-90 fold over PBS primed and OVA primed animals, respectively.

Pharmaceutical composition of escherichia coli heat-labile enterotoxin adjuvant and methods of use

The oral antigens and adjuvants of the present invention are produced in transgenic plants and then administered through the consumption of the transgenic plant. DNA sequences both natural and synthetic encoding for the expression of immunogenic agents which are capable of causing an immune response in animals when fed in edible plants, plant tissues, or derived plant materials are constructed, and plants transformed for stable or transient expression in plant cells. The present invention provides the first known functional method for immunizing animals via transgenic plants, where the plants express bacterial antigens that act as both immunogen and adjuvants when the transgenic plant material expressing the antigens is fed to animals.

Oral immunization with transgenic plants

The present invention is directed towards a novel composition which is a genetically distinct mutant of E. coli heat-labile enterotoxin (LT). Specifically, the mutant LT designated LT(R192G/L211A) is modified by two amino acid substitutions, i.e., the arginine at amino acid position 192 is replaced by glycine and the leucine at amino acid position 211 is replaced by alanine. The invention relates to compositions and methods for use of the novel double mutant of LT as an adjuvant.

Double mutant enterotoxin for use as an adjuvant

Methods and compositions are provided herein for the use of a novel mutant form of E. coli heat-labile enterotoxin which has lost its toxicity but has retained its immunologic activity. This enterotoxin is used in combination with an unrelated antigen to achieve an increased immune response to said antigen when administered as part of an oral vaccine preparation.

Methods and compositions are provided for the cloning and expression of genes coding for the non-toxic subunit of the heat-labile enterotoxin (LT-B) of E. coli. The LT-B thus produced may be formulated for use as an immunogen in vaccines. Specific antibodies produced by this invention may be used in diagnostic tests for the detection of Vibrio cholerae or LT positive enterotoxigenic E. coli. The antibodies of this invention may further be formulated into passive vaccines for the prophylactic or therapeutic protection of human beings or other mammalian species against diarrheal diseases caused by Vibrio cholerae or by the LT positive enterotoxigenic E. coli or other bacteria.

Production of the E. coli LT-B enterotoxin subunit

Methods and compositions are provided for the cloning and expression of plasmids bearing genes coding for the non-toxic subunit of the heat-laible enterotoxin (LT-B) of E. coli. These plasmids may be cloned into stable avirulent strains of Salmonella typhi and used to make oral bivalent vaccines. Such vaccines may be used to prevent typhoid fever and cholera-like enterotoxin-induced diarrheal disease.

Production of the E. coli LT-B enterotoxin subunit in S. typhi

A conjugate, which is the reductive amination product of an immunogenic capsular polymer fragment, having a reducing end and derived from the capsular polymer of a bacterial pathogen, and the non-toxic polypeptide binding subunit of the heat-labile enterotoxin of Escherichia coli (LT-BNT). Also disclosed, are methods for the preparation of the conjugates and for the preparation of vaccines containing the conjugates which elicits an effective level of antibodies in humans. By administering an immunogenic amount of the conjugates, active immunization against systematic infection in young mammals caused by bacterial pathogens can be induced.

Growing community of inventors

New Orleans, LA, United States of America

John D Clements