Los Angeles Biomedical Research Institute at Harbor-ucla Medical Center

Novadigm Therapeutics, Inc.

Ashraf S Ibrahim

John E Edwards, Jr

Yue Fu

Scott G Filler

Brad J Spellberg

Michael R Yeaman

Bradley J Spellberg

Guanpingsheng Luo

Donald Christopher Sheppard

John P Hennessey, Jr

Mingfu Liu

Lin Lin

Priya Uppuluri

Teklegiorgis Ghebremariam

Donald C Sheppard

Sameh Soliman

Shakti Singh

John E Edwards

Disclosed herein are compositions and methods for treating and immunizing againstinfection and colonization. The compositions and methods include polypeptides and fragments derived from theAls3 protein, homologs thereof, and antibodies or fragments thereof that specifically bind these polypeptides and fragments. Administration of these compositions confers treatment and resistance againstinfection and colonization.

Methods of treatment forinfections

Presented herein, in certain aspects, are compositions that comprise novel toxin proteins, the nucleic acids that encode them, and/or portions thereof, which toxins are expressed by fungi of the Mucorales order and are thought to contribute to the pathogenesis of Mucormycosis. Also presented herein, in certain aspects, are methods of detecting the presence or absence of novel fungal toxins and/or the nucleic acids that encode them in a sample, which methods can be used to identify the presence of Mucorales in a subject. Methods and/or compositions presented herein can be used to prevent and/or treat a Mucorales infection.

Fungal toxins and methods related to the same

The invention features a method of vaccinating a mammal againstwhich includes the steps of: a) identifying a mammal at risk for the development of askin or soft tissue infection; and b) administering to said mammal an immunogenic amount of a vaccine that includes a polypeptide including an isolated agglutinin-like sequence (Als) 3 protein (Als3p), or an immunogenic fragment thereof, in a pharmaceutically acceptable medium.

Methods and compositions for vaccinating against

The invention provides a vaccine including an isolated Als protein family member having cell adhesion activity, or an immunogenic fragment thereof, with an adjuvant in a pharmaceutically acceptable medium. The invention also provides a method of treating or preventing hematogenously disseminated or mucocutaneous candidiasis. The method includes administering an immunogenic amount of a vaccine an isolated Als protein family member having cell adhesion activity, or an immunogenic fragment thereof, in a pharmaceutically acceptable medium. A method of treating or preventing disseminated candidiasis also is provided that includes administering an effective amount of an isolated Als protein family member having cell adhesion activity, or an functional fragment thereof, to inhibit the binding or invasion ofto a host cell or tissue. The Als protein family member can be derived from astrain selected from the group consisting ofandand the Als protein family member includes Als1p, Als3p, Als5p, Als6p, Als7p or Als9p. Also provided is a method of treating or preventinginfections. The method includes administering an immunogenic amount of a vaccine an isolated Als protein family member having cell adhesion activity, or an immunogenic fragment thereof, in a pharmaceutically acceptable medium.

Pharmaceutical compositions and methods to vaccinate against disseminated candidiasis and other infectious agents

The disclosure features isolated polypeptides of Hyr1. The disclosure further features vaccines and antibodies useful in treating or preventing candidiasis orinfections or both. Further disclosed are isolated polypeptides consisting of between 14 and 20 amino acids for vaccine preparation. The specific amino acid sequences of isolated polypeptides of Hyr1 are also disclosed.

HYR1-derived compositions and methods of treatment using same

The invention features fragments of thecell surface proteins Als3 and Hyr1 and combinations thereof useful in immunizing a subject against fungal or bacterial infections or both.

Compositions and methods for treating fungal and bacterial pathogens

Abloodstream infections cause significant morbidity and mortality in hospitalized patients. Filament formation and adherence to host cells are critical virulence factors of. Multiple filamentation regulatory pathways have been discovered, however the downstream effectors of these regulatory pathways remain unknown. The cell surface proteins in the ALS group are downstream effectors of the filamentation regulatory pathway. Particularly, Als1p mediates adherence to endothelial cells in vitro and is required for virulence. The blocking of adherence by the organism is described resulting from the use of a composition and method disclosed herein. Specifically, a pharmaceutical composition comprised of a gene, gene product, or specific antibody to the ALS gene family is administered as a vaccine to generate an immune response capable of blocking adherence of the organism.

Pharmaceutical compositions and methods to vaccinate against candidiasis

The invention provided Mucorales CotH polypeptides and encoding nucleic acid molecules. The Mucorales CotH polypeptides and encoding nucleic acids can be advantageously used to diagnose, treat or prevent fungal conditions, in particular mucormycosis.

Immunotherapy and diagnosis of mucormycosis using CotH

The present invention provides therapeutic compositions and methods for treating and preventing fungal disease or conditions including mucormycosis. The therapeutic methods and compositions of the invention include antibody, antibody fragment, siRNA and vaccine compositions having or directed against a GRP78 polypeptide or an antigenic fragment of the polypeptide.

Mammalian receptors as targets for antibody and active vaccination therapy against mold infections

The invention is based, in part, on the discovery of a novel cell-based immunotherapy that can recapitulate neutrophil functions in neutropenic individuals afflicted with a microbial infection. The therapeutic methods of the invention are broadly applicable to treat any infection in a neutropenic individual, including infections caused by bacteria, fungi, protozoa, and viruses. The methods of the invention represent a practical, rapid cell-based immunotherapy for refractory infections comprising compositions of activated, irradiated HL-60 cells.

Methods for treating refractory infections in neutropenic individuals

The present invention provides vaccine compositions comprising OmpA, or antigenic fragments thereof, and related methods of active immunization againstinfection. The invention also provides antibodies and antigen-binding parts thereof that specifically bind to OmpA, and related methods of passive immunization againstinfection. The compositions and methods of the invention are useful for preventing or treatinginfections, including those caused by strains resistant to carbapenems and all other antibiotics except colistin or tigecycline, also referred to as extreme drug resistant (XDR)infections, and those resistant to every FDA approved antibiotic, also referred to as pan-drug resistant (PDR)infections.

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The invention features HYR1 as a vaccine target and as a prophylactic strategy for combating disseminated candidiasis.

The present invention provides therapeutic compositions and methods for treating and preventing fungal disease or conditions including mucormycosis. The therapeutic methods and compositions of the invention include vaccine compositions having an FTR polypeptide or an antigenic fragment of the polypeptide; a vector including a nucleotide sequence that is substantially complimentary to at least 18 contiguous nucleotides of FTR sequence; an antisense; a small interfering RNA or an antibody inhibitor of FTR. The vaccine compositions of the invention can further include an adjuvant.

Vaccine compositions and methods for treatment of mucormycosis and other fungal diseases

Abloodstream infections cause significant morbidity and mortality in hospitalized patients. Filament formation and adherence to host cells are critical virulence factors of. Multiple filamentation regulatory pathways have been discovered, however the downstream effectors of these regulatory pathways remain unknown. The cell surface protein, Als1p, is a downstream effector of the filamentation regulatory pathway and is regulated by Efg1p. Als1p mediates adherence to endothelial cells in vitro and is required for virulence. The blocking of adherence by the organism is described resulting from the use of a composition and method disclosed herein. Specifically, a pharmaceutical composition comprised of a gene product from the ALS1 gene family is administered as a vaccine to generate an immune response capable of blocking adherence of the organism.

Growing community of inventors

Irvine, CA, United States of America

Ashraf S Ibrahim