Albert Einstein College of Medicine

The Brigham and Women's Hospital, Inc.

Vaccinex, Inc.

University of California

The University of North Carolina at Chapel Hill

Colorado State University Research Foundation

Steven A Porcelli

Michael B Brenner

William R Jacobs, Jr

Evan M Beckman

Maurice Zauderer

Miriam Braunstein

Stephen T Furlong

Robert L Modlin

Tsungda Hsu

Patrick Joseph Brennan

William R Jacobs

John Chan

Volker Briken

Peter A Sieling

Dee Dao

Kari Sweeney

Manjunatha M Venkataswamy

William R Jacob

The invention is directed to compositions and methods related to proteins that are physically associated with ceramide-like glycolipids for use as activators of NKT cells. The compositions and methods of the present invention are useful for the prevention and treatment of diseases.

Modified glycolipids and methods of making and using the same

The invention is directed compositions and methods related to bacterial cells physically associated with ceramide-like glycolipids. The invention allows for delivery of ceramide-like glycolipid adjuvants directly to the same cells that become infected with a bacterial vaccine. The compositions and methods of the present invention are useful for the prevention and treatment of diseases.

Bacterial vaccines with cell wall-associated ceramide-like glycolipids and uses thereof

Provided are mycobacteria deleted in at least a portion of a region 3 ESAT-6-like gene cluster. Also provided are mycobacteria comprising a mutation in an roc-1 gene. Additionally, vaccines comprising these mycobacteria are provided. Further provided are methods of making a recombinant, methods of inducing an immune response in a mammal, methods of inhibiting IL-12 production in a mammal, and methods of stimulating IL-12 production in a mammal. Vaccine adjuvants are also provided, as are methods of inducing immunity to a target antigen in a mammal.

Mycobacterial mutants inducing IL-12

Provided are recombinanthaving a mutation in an nlaA gene or in a nuoG gene. Also provided are isolated and purified nlaA proteins and nuoG proteins from a. Additionally provided are isolated and purified nucleic acids comprising a recombinant nlaA gene or a recombinant nuoG gene. Further provided are methods of inducing an immune response in a mammal and methods of making a recombinantusing the nlaA gene or the nuoG gene.

Mycobacterial mutants affecting host apoptosis

Provided are mycobacteria comprising (a) a mutation that is not in a SecA2 gene that attenuates the virulence of the mycobacteria in a mammalian host, and (b) a mutation in a SecA2 gene that eliminates SecA2 activity. Also provided are mycobacteria that comprise a mutation in a SecA2 gene that eliminates SecA2 activity, where the mycobacteria are notor. Additionally provided are methods of inducing an immune response in a mammal and methods of inducing an immune response to a pathogenicin a human using the above mycobacterial mutants.

Mycobacterial SecA2 mutants

&#x3b1;-Galactosylceramides and glycosylceramides ('ceramide-like glycolipids') that modulate NK T cells. The ceramide-like glycolipids vary in the cytokines induced in NK T cells and vary in the antigen-presenting cells that are capable of efficiently presenting the compounds to NK T cells. Pharmaceutical compositions of the ceramide-like glycolipids are provided, as are pharmaceutical compositions of the ceramide-like glycolipids combined with dendritic cells. Methods utilizing the ceramide-like glycolipids in vaccines, to activate NK T cells, to stimulate the immune system, and to treat mammals are also provided. The invention also provides methods of evaluating a compound for its ability to activate an NK T cell in the presence of a cell expressing a CD1d protein.

Ceramide derivatives as modulators of immunity and autoimmunity

Provided are CD-1 presented antigens, compositions, cells, inhibitors and methods relating to the use of hydrophobic antigen presentation by CD1 molecules, including: methods for detecting the presence of a CD1-presented hydrophobic antigen in a sample; methods for isolating such CD1-presented antigens and isolated antigens; vaccines containing CD1-presented antigens and vaccination methods; methods of blocking CD1 antigen presentation; methods of identifying and/or isolating CD1 blocking agents and the isolated CD1 blocking agents; methods of inducing CD1 expression; and T-cells for use in the methods disclosed herein.

Presentation of hydrophobic antigens to T-cells by CD1 molecules

The present invention is based on the observation that CD1 functions to present foreign and autoimmune antigens to a select subpopulation of T-cells. Based on this observation, the present invention provides methods for detecting the presence of a CD1-presented antigen in a sample, methods for purifying CD1-presented antigens, vaccines containing CD1-presented antigens, methods of blocking CD1 antigen presentation, methods of identifying and/or isolating CD1 blocking agents, methods of inducing CD1 expression, and T-cell lines for use in the methods disclosed herein. The CD1-presented antigens of the invention, unlike MHC-presented antigens, are non-polypeptide hydrophobic antigens. In particular, a CD1-presented antigen isolated from several mycobacterial species is a lipoarabinomannan (LAM).

Method for inducing a CD1-restricted immune response

The present invention is based on the observation that CD1 functions to present foreign and autoimmune antigens to a select subpopulation of T-cells. Based on this observation, the present invention provides methods for detecting the presence of a CD1-presented antigen in a sample, methods for purifying CD1-presented antigens, vaccines containing CD1-presented antigens, methods of blocking CD1 antigen presentation, methods of identifying and/or isolating CD1 blocking agents, methods of inducing CD1 expression, and T-cell lines for use in the methods disclosed herein. The CD1-presented antigens of the invention, unlike MHC-presented antigens, are non-polypeptide hydrophobic antigens. In particular, a CD1-presented antigen isolated from several mycobacterial species is a mycolic acid (MA).

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Bronx, NY, United States of America

Steven A Porcelli