The Rockefeller University

New York University

City University of New York

The Scripps Research Institute

Sanaria Inc.

Aaron Diamond Aids Research Center

Moriya Tsuji

Chi-Huey Wong

David D Ho

Masakazu Fujio

Richard W Franck

Guangli Yang

Douglass Wu

Xiangming Li

Guangwu Chen

Stephen L Hoffman

Sumana Chakravarty

David G Ho

Yaoxing Huang

Yasuhiko Koezuka

Takayuki Shiratsuchi

John Schmieg

Doug Wu

Gloria Gonzalez-Aseguinolaza

Disclosed herein are pharmaceutical compositions comprisingsporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host rangeand analogues of &#x3b1;-galactosylceramide (&#x3b1;-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided.

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The present disclosure relates to adenovirus protein modifications to augment immune response to a transgene of a recombinant adenovirus and to circumvent pre-existing anti-adenovirus immunity. Some embodiments are directed to a recombinant adenovirus derived from a recombinant adenovirus plasmid vector, wherein the recombinant adenovirus plasmid vector comprises a nucleotide sequence encoding acircumsporozoite protein, or antigenic portion thereof, operably linked to a heterologous promoter and a modified capsid or core protein, wherein an immunogenic epitope ofcircumsporozoite is inserted into or replaces at least part of a capsid or core protein. Other embodiments are directed to a pharmaceutical composition or a malaria vaccine composition comprising a recombinant adenovirus according to the above embodiments. Further embodiments include a method of treating, preventing, or diagnosing malaria, comprising administering a therapeutic amount of the pharmaceutical composition or malaria vaccine composition in accordance with the above embodiment.

Modification of recombinant adenovirus with immunogenic plasmodium circumsporozoite protein epitopes

The present invention is directed to the discovery that allogenic or syngenic adjuvant stimulation can cause local inflammation which increases the antigen presentation capability of cells in the vicinity of adjuvant stimulation. By discovering this phenomenon, the present invention provides a novel method for augmenting the immunogencity of an antigen by conjointly administering an allogenic or syngenic MHC molecule (as a universal adjuvant) to trigger a local inflammatory reaction to enhance antigen presentation at the site of delivery.

Use of allogenic or syngenic major histocompatibility complex (MHC) molecules as universal adjuvants for vaccines against neoplastic disease, infection and autoimmune disease

The invention is directed to novel synthetic C-glycolipids that selectively induce a ThI-type immune response characterized by enhanced IL-12 secretion and increased activation of dendritic cells. The compounds of the invention are thereby useful in treating infections, cancers, cell proliferative disorders, and autoimmune diseases, both directly and as adjuvants.

C&#x2014;glycolipids with enhanced Th-1 profile

This invention relates to immunogenic compounds which serve as ligands for NKT (natural killer T) cells and to methods of use thereof in modulating immune responses.

Glycolipids and analogues thereof as antigens for NKT cells

The invention is directed to compounds of formula (I) wherein X is O or NH; R' is a hydrocarbon chain; Rand Rare hydrogen, OH or a monosaccharide; Ris hydrogen or a monosaccharide; Q&#x2032; is optionally present and may be a Chydrocarbon; X&#x2032; is optionally present and may be O, S or NR; and Qmay be a hydrocarbon or hydrogen. The invention is also directed to the use of the compounds for treating cancer, infectious diseases and autoimmune diseases. The invention is also directed to syntheses of the compounds of formula (I).

Synthetic C-glycolipid and its use for treating cancer, infectious diseases, and autoimmune diseases

The present invention relates to methods and compositions for augmenting an immunogenicity of an antigen in a mammal, comprising administering said antigen together with an adjuvant composition that includes a synthetic glycolipid compound of Formula I, as described herein. According to the present invention, the use of a compound of Formula I as an adjuvant is attributed at least in part to the enhancement and/or extension of antigen-specific Th1-type responses, in particular, CD8+ T cell responses. The methods and compositions of the present invention can be useful for prophylaxis and treatment of various infectious and neoplastic diseases.

Use of synthetic glycolipids as universal adjuvants for vaccines against cancer and infectious diseases

This invention relates to immunogenic compounds which may serve as ligands for NKT (natural killer T) cells and to methods of use thereof in modulating immune responses.

Glycolipids and analogues thereof as antigens for NK T cells

The present invention relates to methods and compositions for augmenting an immunogenicity of an antigen in a mammal, comprising administering said antigen together with an adjuvant composition that includes glycosylceramide, preferably &#x3b1;-galactosylceramide (&#x3b1;-GalCer). According to the present invention, the use of glycosylceramide as an adjuvant is attributed at least in part to the enhancement and/or extension of antigen-specific Th1-type responses, in particular, CD8+ T cell responses. The methods and compositions of the present invention can be useful for prophylaxis and treatment of various infectious and neoplastic diseases.

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New York, NY, United States of America

Moriya Tsuji