University System of Maryland

Aeras Global Tb Vaccine Foundation

Crucell Holland B.v.

Other

Leland Stanford Junior University

David M Hone

Jerald C Sadoff

George K Lewis

Robert J Powell

Ronggai Sun

Richard Crowley

Ronald Vogels

Katarina Radosevic

Menzo Jans Emco Havenga

David Onyabe

Yasir Abdul Wahid Skeiky

Yasir A W Skeiky

Gary K Schoolnik

Menzo J E Havenga

John Fulkerson

Timothy R Fouts

Mohamed Tarek Shata

Michele Stone

Mario Alberto Flores-Valdez

Michel Klein

Yasir Abdul Skeiky

Menzo Jans Havenga

M Tarek Shata

Christine Obriecht

Ken Bagley

Simon Agwale

Michael Boysen

Mt Shata

Michael Boyson

The invention relates to vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding for at least two antigens from one or more tuberculosis-causing bacilli. Also described is the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. Further described is the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.

Multivalent vaccines comprising recombinant viral vectors

Described are vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding at least two antigens from one or more tuberculosis-causing bacilli. Also described is the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. Also described is the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.

Bacterial packaging strains useful for generating recombinant double-stranded RNA nucleocapsids (rdsRNs) are provided. The packaging strains are useful for the production of RNA encoding vaccine antigens, bioactive proteins, immunoregulatory proteins, antisense RNAs, and catalytic RNAs in eukaryotic cells or tissues. Recombinant ssRNA is introduced into the strains and packaged to form rdsRNs de novo.

Bacterial packaging strains useful for generation and production of recombinant double-stranded RNA nucleocapsids and uses thereof

strains that have an enhanced ability to elicit a MHC-Class I-restricted CD8T cell immune response are provided. Thestrains are genetically engineered to express: a endosomalytic protein that is active at neutral pH (e.g. Perfringolysin O), permitting escape of thefrom endosomes into the cytoplasm of the cell; and antigens of interest, such as tuberculosis antigens. The invention also provides vaccine preparations containing suchstrains.

Recombinant BCG strains with enhanced ability to escape the endosome

The invention relates to vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding for at least two antigens from one or more tuberculosis-causing bacilli. The invention also relates to the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. The invention furthermore relates to the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.

A vaccine for treating or preventing the establishment of latent tuberculosis infections is provided. The vaccine comprises a recombinantthat overexpresses the transcription factor DosR, at a level sufficient to induce production of the dosR regulon genes or proteins. A host to whom the vaccine is administered mounts an immune response to the dosR regulon proteins and is thus protected from the establishment, persistence or reactivation of latent tuberculosis.

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A recombinant double stranded RNA (dsRNA) nucleocapsid useful for the expression of dsRNA expression cassettes encoding passenger genes, such as, but not restricted to, vaccine antigens, bioactive proteins, immunoregulatory proteins, antisense RNAs, and catalytic RNAs, replicates in bacterial hosts and includes a P8 protein shell and three dsRNA segments where one of the segments includes a cap independent translation enhancer (CITE) operationally linked to a passenger gene.

Recombinant double stranded RNA nucleocapsid and use of the same

Recombinantstrains with improved vaccinal properties for use as vaccinating agents are provided. The parent strains of the recombinantstrains are selected for their potent immunogenicity. Thestrains do not display antibiotic resistance, and do not exhibit horizontal transfer to gram-negative bacteria.

strains that have an enhanced ability to elicit a MHC-Class I-restricted CD8T cell immune response are provided. Thestrains are genetically engineered to express: a endosomolytic protein that is active at neutral pH (e.g. Perfringolysin O), permitting escape of thefrom endosomes into the cytoplasm of the cell; and antigens of interest, such as tuberculosis antigens. The invention also provides vaccine preparations containing suchstrains.

Transformed bacterium lacking selectable marker and overexpression of antigens in mycobacteria

A recombinant double stranded RNA (dsRNA) phage expresses dsRNA-encoded genes in eukaryote cells. Recombinant dsRNA phage are useful for the expression of dsRNA expression cassettes encoding passenger genes, such as, but not restricted to, vaccine antigens, bioactive proteins, immunoregulatory proteins, antisense RNAs, and catalytic RNAs in eukaryotic cells or tissues. Methods are provided to deliver recombinant dsRNA phage to eukaryotic cells and tissues, either by direct administration, formulated in lipid or polylactide-coglycolide, or by utilizing a bacterial vaccine vector.

Recombinant double-stranded RNA phage, and use of the same

HIV envelope immunogens that display multivalent epitopes are provided. The immunogens are aggregated, 'webbed' HIV envelope immunogens in which native envelope structures are stabilized due to interactions with multimeric derivatives of M9 scorpion toxin.

Webbed immunogens comprising recombinant human immunodeficiency virus (HIV) envelope glycoproteins and the M9 scorpion toxin

The present invention provides recombinant double stranded RNA phages (rdsRP) that express dsRNA-encoded genes in eukaryote cells. Recombinant dsRNA phages are useful for the expression of dsRNA expression cassettes encoding passenger genes, such as, but not restricted to, vaccine antigens, bioactive proteins, immunoregulatory proteins, antisense RNAs, and catalytic RNAs in eukaryotic cells or tissues. Methods are provided to deliver a recombinant dsRNA phage to eukaryotic cells and tissues, either by direct administration, formulated in lipid or polylactidecoglycolide, or by utilizing a bacterial vaccine vector.

Recombinant double-stranded RNA phages and uses thereof

A method for introducing and expressing genes in animal cells is disclosed comprising infecting said the animal cells with live invasive bacteria, wherein bacteria contain a eukaryotic expression cassette encoding said gene. The gene may encode, e.g., a vaccine antigen, an therapeutic agent, an immunoregulatory agent or a anti-sense RNA or a catalytic RNA.

Method for introducing and expressing genes in animal cells, and live invasive bacterial vectors for use in the same

A method for introducing and expressing genes in animal cells, in which the animal cells are transfected with bacterial blebs containing a eukaryotic expression cassette encoding the gene. Bacterial blebs comprising a eukaryotic expression cassette, wherein the bacterial blebs are derived from gram negative bacteria.

Growing community of inventors

Ellicott City, MD, United States of America

David M Hone