Institute for Systems Biology

University of Washington

Emory University

University of Cape Town

Seattle Children's Hospital

Seattle Children's Hospital Dba Seattle Children's Research Institute

Alan Arnold Aderem

Adrian Ozinsky

Fumitaka Hayashi

David M Underhill

Kelly D Smith

Carl L Hansen

Baozhong Wang

Ioanna Skountzou

Thomas Jens Scriba

Daniel Edward Zak

Ethan Greene Thompson

Richard L Compans

Adam Garth Penn-Nicholson

Willem Albert Hanekom

Jadranmka Boza

Carrie M Rosenberger

Alan Diercks

This invention relates to a prognostic method for determining the risk of an asymptomatic human subject with latent tuberculosis (TB) infection or apparent latent TB infection and/or after suspected exposure to TB progressing to active tuberculosis disease comprising the steps of quantifying and computationally analysing relative abundances of a collection of pairs of gene products ('TB biomarkers') derived from a sample obtained from the subject. The invention further relates to a collection of TB biomarkers that generates a transcriptomic signature of risk for prediction of the likelihood of an asymptomatic human subject with latent TB infection and/or after suspected exposure to TB progressing to active tuberculosis disease. Furthermore, a kit comprising gene-specific primers or oligonucleotide probes for the detection of pairs of TB biomarkers that generates a prognostic signature of risk for use with the method of the invention is described. In addition, the invention relates to a method of preventive treatment or prophylaxis for TB infection comprising the use of the prognostic method and/or the kit of the invention to select an appropriate or experimental treatment regime or intervention for the human subject and/or to monitor the response of the human subject to the TB prophylaxis.

Biomarkers for prospective determination of risk for development of active tuberculosis

Embodiments of the disclosure encompass compositions and methods for generating immune responses in an animal or human host. Embodiments of the compositions encompass proteins derived from the surface proteins of bacteria and protozoa, and in particular the flagellum component flagellin, and which have adjunctival properties when administered in conjunction with an immunogen. Embodiments of the compositions of the disclosure are modified to incorporate a heterologous transmembrane-cytoplasmic domain allowing the peptides to be incorporated into virus-like particles. Embodiments of the methods of generating an immunological response in an animal or human comprise exposing the immune system of an animal or human host to an immunogen and a virus-like particle comprising an adjuvant polypeptide including a host cell Toll-like receptor ligand polypeptide having a transmembrane-cytoplasmic tail polypeptide, and a heterologous signal peptide.

Immunogenic compositions and methods of use thereof

The invention provides methods to elicit an immune response with an immunomodulatory flagellin polypeptide having toll-like receptor 5 (TLR5) binding, and further comprising an ADCC targeting molecule.

Toll-like receptor 5 ligands and methods of use

The invention is directed to an improved method to manufacture virus for use in vaccine by culturing infected cells that have been modified to overexpress miR-144. The invention is also directed to manipulating the activity or level of miR-144 in subjects in order to modulate the antiviral and immune response systems.

Methods and compositions to modulate antiviral and immune activity responses

The invention provides an immunomodulatory flagellin peptide having substantially the same amino acid sequence GALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQ (SEQ ID NO:44), or a modification thereof, and having toll like receptor 5 (TLR5) binding. The immunomodulatory flagellin peptide also can have substantially the same amino acid sequence TQFSGVKVLAQDNTLTIQVGANDGETIDIDLKQINS QTLGLDTL (SEQ ID NO:45); EGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRLNEIDRVNG (SEQ ID NO:46) or MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANF TANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQS (SEQ ID NO:47), or a modification thereof. Also provided is an immunomodulatory flagellin peptide having substantially the same amino acid sequence LQKIDAALAQVDTLRSDLGAVQNRFNSAITNL (SEQ ID NO:48), or a modification thereof, and having toll like receptor 5 (TLR5) binding. The immunomodulatory flagellin peptide also can have substantially the same amino acid sequence TLRSDLGAVQNRFNSAITNLGNTVNNLSS (SEQ ID NO:49) or EQAAKTTENPLQKIDAALAQVDTLRSDLGAVQNRFNSAITNLGNTVNNLSS (SEQ ID NO:50), or a modification thereof. Further provided is an immunomodulatory flagellin peptide having substantially the same amino acid sequence GALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAE ITQ (SEQ ID NO:44) and substantially the same amino acid sequence LQKIDAALAQVDTLRSDLGAVQNRFNSAITNL (SEQ ID NO:48), or a modification thereof, and having toll like receptor 5 (TLR5) binding. Methods of using immunomodulatory flagellin peptides additionally are provided.

Microfluidic systems are disclosed, including microfluidic devices and methods, useful for simultaneously analyzing multiple analytes in each of a plurality of distinct nanoliter-volume samples.

Multiplexed, microfluidic molecular assay device and assay method

The invention provides an immunomodulatory flagellin peptide having at least about 10 amino acids of substantially the amino acid sequence GAVQNRFNSAIT (SEQ ID NO:2), or a modification thereof, and having toll-like receptor 5 (TLR5) binding. Methods of inducing an immune response are also provided.

Growing community of inventors

Seattle, WA, United States of America

Alan Arnold Aderem