Vaccines and methods for prevention and treatment of drug-resistant HIV-1 and hepatitis B virus

The present invention provides methods for lowering a viral load of a virus resistant to an antiviral drug by inducing cytotoxic T lymphocytes (CTL) to recognize a predetermined mutated epitope within a viral protein of the drug-resistant virus. CTLs are induced by immunizing a host with a peptide comprising the predetermined mutation. The immunostimulating peptide may be further improved by epitope-enhancement for inducing specific CTLs. The antiviral protection against drug-resistant virus shown by compositions of the present invention and mediated by human HLA-restricted CTL has not been previously achieved.

Immunostimulatory combinations of TLR ligands and methods of use

The present invention provides immunostimulatory combinations of TLR ligands and therapeutic and/or prophylactic methods that include administering an immunostimulatory combination to a subject. In general, the immunostimulatory combinations described herein can provide an increased immune response compared to other immunostimulatory combinations and/or compositions.

Beta-mannosylceramide and stimulation of NKT cell anti-tumor immunity

β-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of α-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising β-mannosylceramide, as well as methods of treatment of tumors are also provided.

MULTI-EPITOPE TARP PEPTIDE VACCINE AND USES THEREOF

Immunogenic T cell receptor γ alternate reading frame protein (TARP) peptide compositions that include multiple epitopes of the TARP protein are described. The disclosed compositions can be used for the treatment of TARP-expressing cancers, such as prostate cancer, breast cancer and mesothelioma. In some embodiments, the TARP peptide compositions disclosed herein include sets of overlapping TARP peptides that each have a length of about 15 to about 25 amino acids, and comprise about 5 to about 15 amino acids that are identical to at least another overlapping peptide in the set. In particular examples, the combination of the overlapping TARP peptides in the set encompasses the complete amino acid sequence of human TARP. The multi-epitope peptide compositions described herein include both CD4 and CD8 epitopes, a feature that is important for eliciting CD4 T cell and CD8 T cell, as well as humoral, immune responses. 1. A composition comprising at least two non-identical overlapping T cell receptor γ alternate reading frame protein (TARP) peptides , wherein the amino acid sequences of the at least two overlapping TARP peptides consist of 15 to 25 consecutive amino acids of SEQ ID NO: 1 or SEQ ID NO: 2 , and wherein each of the at least two overlapping TARP peptides comprises 5 to 15 consecutive amino acids that are identical to at least another of the overlapping TARP peptides.2. The composition of claim 1 , comprising three claim 1 , four claim 1 , five claim 1 , six or seven overlapping TARP peptides.3. The composition of claim 1 , comprising five overlapping TARP peptides claim 1 , wherein the amino acid sequences of the five overlapping TARP peptides consist of 18 to 20 consecutive amino acids of SEQ ID NO: 1 claim 1 , and wherein each of the five overlapping TARP peptides comprises 10 consecutive amino acids that are identical to at least one other of the overlapping TARP peptides.4. The composition of claim 3 , wherein the combination of the five overlapping TARP ...

IMMUNOSTIMULATORY COMBINATIONS OF TLR LIGANDS AND METHODS OF USE

The present invention provides immunostimulatory combinations of TLR ligands and therapeutic and/or prophylactic methods that include administering an immunostimulatory combination to a subject. In general, the immunostimulatory combinations described herein can provide an increased immune response compared to other immunostimulatory combinations and/or compositions. 178-. (canceled)79. An immunostimulatory composition for inducing high functional avidity T cells comprising an effective amount of a triple combination of TLR agonists which synergistically activate IL-15 and IL-12 production of dendritic cells as compared to a double combination of TLR agonists thereby inducing high functional avidity T cells.80. The immunostimulatory composition of claim 79 , wherein the triple combination of TLR agonists comprises a TLR2 claim 79 , TLR3 claim 79 , and TLR9 agonist.81. The immunostimulatory composition of claim 80 , wherein the TLR2 agonist is MALP-2 claim 80 , the TLR3 agonist is polyl:C claim 80 , and the TLR9 agonist is CpG.82. The immunostimulatory composition of further comprising one or more antigens.83. The immunostimulatory composition of wherein the antigen is conjugated to a TLR agonist.84. An immunostimulatory composition according to that is effective for inducing an immune response to the antigen in a subject immunized with the immunostimulatory composition.85. The immunostimulatory composition according to wherein the antigen comprises a tumor antigen claim 79 , a viral antigen claim 79 , a bacterial antigen claim 79 , a fungal antigen claim 79 , a parasitic antigen claim 79 , an alloantigen claim 79 , or a xenoantigen.86. A method of activating dendritic cells (DCs) to form high functional avidity T cells in a subject comprising administering to the subject an effective amount of a immunostimulatory composition comprising an effective amount of a triple combination of TLR agonists which synergistically activates IL-15 and IL-12 production of the ...

Beta-mannosylceramide and stimulation of nkt cell anti-tumor immunity

β-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of α-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising β-mannosylceramide, as well as methods of treatment of tumors are also provided.

Immunogenic pote peptides and methods of use

POTE has recently been identified as a tumor antigen expressed in a variety of human cancers, including colon, ovarian, breast, prostate, lung and pancreatic cancer. Described herein are immunogenic POTE polypeptides, including modified POTE polypeptides, that bind MHC class I molecules. The immunogenic POTE polypeptides are capable of inducing an immune response against POTE-expressing tumor cells. Thus, provided herein is a method of eliciting an immune response in a subject, such as a subject having a type of cancer that expresses POTE.

Immunogenic Peptides of Xage-1

XAGE-1 is a gene expressed in a number of important human cancers, including prostate cancer, lung cancer, breast cancer, ovarian cancer, glioblastoma, pancreatic cancer, and melanoma. It has now been discovered that peptides of fifty or fewer amino acids comprising the sequence XXXPSAPSPX(SEQ ID NO:5), where Xis any amino acid and is preferably G or Y; Xis selected from the group consisting of L, M, A, I, V, and T, with L and M being preferred; Xis a hydrophobic residue, M or A; and Xis V, M, L, A, I, or T, and is preferably V, bind to the HLA-A2 MHC class I molecule, and can be used to raise immune responses to XAGE-1-expressing cancers. In some embodiments, the P at position 7, the S at position 8, or the P at position 9, can be omitted to create a 9 amino acid peptide. The invention provides immunogenic peptides, nucleic acids encoding them, vectors comprising the nucleic acids, uses of the peptides and nucleic acids for manufacture of medicaments, methods of using the peptides and nucleic acids, and compositions of the peptides or nucleic acids in pharmaceutically acceptable carriers. 1. An isolated immunogenic peptide of 50 or fewer amino acids comprising an amino acid sequence XXXPSAPSPX(SEQ ID NO:5) , wherein:{'sub': '1', 'Xcan be any amino acid;'}{'sub': '2', 'Xcan be L, M, A, I, V, or T;'}{'sub': '3', 'Xcan be a hydrophobic residue, methionine or alanine; and'}{'sub': '4', 'Xcan be V, M, L, A, I, or T.'}2. An immunogenic peptide of claim 1 , wherein Xis tyrosine (SEQ ID NO:34).3. An immunogenic peptide of claim 1 , wherein Xis leucine (SEQ ID NO:35).4. An immunogenic peptide of claim 1 , wherein Xis methionine (SEQ ID NO:36).5. An immunogenic peptide of claim 1 , wherein Xis valine (SEQ ID NO:37).6. An immunogenic peptide of claim 1 , which peptide comprises an amino acid sequence selected from the group consisting of GVFPSAPSPV (SEQ ID NO:6) claim 1 , YVFPSAPSPV (SEQ ID NO:7) claim 1 , GLFPSAPSPV (SEQ ID NO:8) claim 1 , GVMPSAPSPV (SEQ ID NO:9) claim 1 , ...

Immunogenic pote peptides and methods of use

POTE has recently been identified as a tumor antigen expressed in a variety of human cancers, including colon, ovarian, breast, prostate, lung and pancreatic cancer. Described herein are immunogenic POTE polypeptides, including modified POTE polypeptides, that bind MHC class I molecules. The immunogenic POTE polypeptides are capable of inducing an immune response against POTE-expressing tumor cells. Thus, provided herein is a method of eliciting an immune response in a subject, such as a subject having a type of cancer that expresses POTE.

3-O-SULFO-GALACTOSYLCERAMIDE ANALOGS AS ACTIVATORS OF TYPE II NKT CELLS AND USES THEREOF

Disclosed is a compound of the formula (I) or (II): wherein a f are as described herein. The compounds are useful in the activation of Type II NKT cells and in treating cancer. 8. A composition comprising a compound claim 1 , salt claim 1 , solvate claim 1 , stereoisomer claim 1 , or mixture comprising stereoisomers of and a pharmaceutically acceptable carrier.9. The composition of further comprising a therapeutically effective amount of an α-galactosylceramide or a salt or solvate thereof.10. The composition of further comprising granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or one or more cytokines that induce cellular immunity.11. The composition of claim 10 , wherein the one or more cytokines that induce cellular immunity comprises interleukin (IL)-12 and/or IL-15.12. The composition of claim 8 , further comprising at least one T-cell co-stimulatory molecule selected from the group consisting of B7-1 claim 8 , B7-2 claim 8 , B7-3 claim 8 , B7-H claim 8 , Intercellular Adhesion Molecule (ICAM) 1 claim 8 , ICAM2 claim 8 , ICAM3 claim 8 , LFA1 claim 8 , LFA2 claim 8 , LFA3 claim 8 , CD40L claim 8 , OX40L and 4-1BBL.13. The composition of claim 8 , further comprising at least one Toll-like Receptor (TLR) ligand.14. The composition of claim 13 , wherein the at least one TLR ligand is a ligand for a molecule selected from the group consisting of TLR2 claim 13 , TLR3 claim 13 , TLR4 claim 13 , TLR5 claim 13 , TLR7 claim 13 , TLR8 claim 13 , and TLR9.15. The composition of claim 8 , further comprising a vaccine.16. The composition of wherein the vaccine comprises one or more T cell receptor gamma alternate reading frame protein (TARP) peptides selected from the group consisting of 29-37-9V claim 15 , 27-35 claim 15 , 1-20 claim 15 , 11-30 claim 15 , 21-40 claim 15 , 31-50 and 41-58 in combination with Sargramostin (GM-CSF) emulsified in Montanide ISA 51 VG.17. The composition of claim 8 , further comprising an antibody.18. The composition of claim 17 , ...

BIOMARKER ANALYSIS FOR HIGH-THROUGHPUT DIAGNOSTIC MULTIPLEX DATA

Flow cytometry of extracellular vesicle (EV) samples produces counts associated with channels defined by combinations of capture agents and detection agents, typically capture antibodies and detection antibodies having associated markers such as fluorophores. Sample groupings are obtained by processing channel counts using principal component analysis or other techniques. Identification of a particular sample grouping permits selection of associated channels for detection of samples exhibiting characteristics of the particular sample grouping. 1. A method , comprising:obtaining multichannel flow cytometry channel counts for a plurality of extracellular vesicle (EV) samples for each of a plurality of channels, each channel defined by a capture agent and a detection agent; andwith a processor, identifying at least two groups of samples exhibiting differing states based on the multichannel flow cytometry channel counts.2. The method of claim 1 , further comprising displaying a heat map based on the channel counts for each of the plurality of channels.3. The method of claim 1 , wherein the channel counts for each of the plurality of channels are representable as a stored heat map claim 1 , and the further comprising deriving a dendogram based on a hierarchical clustering associated with the stored heat map.4. The method of claim 3 , further comprising:displaying the derived dendogram; andbased on the derived dendogram, identifying the at least two groups of samples.5. The method of claim 2 , further comprising:obtaining principal component scores and coefficients based on the heat map; andidentifying the at least two groups of samples based on the principal component scores and coefficients.6. The method of claim 5 , further comprising displaying the principal component scores claim 5 , wherein the at least two groups of samples are identified based on the displayed principal component scores.7. The method of claim 6 , wherein the display of the principal component ...

IMMUNOGENIC PEPTIDES AND METHODS OF USE FOR TREATING AND PREVENTING CANCER

Disclosed are immunogenic peptides, related fusion proteins, nucleic acids encoding the peptides or fusion proteins, conjugates, expression vectors, host cells, and antibodies. Also, disclosed are pharmaceutical compositions, vaccines for use in the treatment or prevention of cancer, e.g., alveolar rhabodomyosarcoma, methods of stimulating a T cell to kill a tumor cell, methods of stimulating CD4 and CD8 T cells, and methods of treating or preventing cancer are further provided herein. 1. An immunogenic peptide comprising(a) the amino acid sequence SPQNSIRHNL (SEQ ID NO: 3), a functional portion or functional variant thereof, or a pharmaceutically acceptable salt thereof, wherein the peptide, or functional portion or functional variant thereof, binds to an MHC Class I molecule, provided that the peptide does not consist of the amino acid sequence TIGNGLSPQNSIRHNLSL (SEQ ID NO: 4) or NPTGTIGNGLSPQNSIRHNLSLH (SEQ ID NO: 5), wherein the peptide of (a) is isolated; or(b) an immunogenic peptide comprising SEQ ID NO: 3 with an alanine substitution at the third, fifth, or sixth position of SEQ ID NO: 3, a functional portion thereof, or a pharmaceutically acceptable salt thereof, wherein the peptide or functional portion thereof binds to an MHC Class I molecule.214-. (canceled)15. A fusion protein comprising the immunogenic peptide of and an MHC Class I molecule claim 1 , or a functional portion thereof.16. (canceled)17. A conjugate comprising the immunogenic peptide of .1822-. (canceled)23. An isolated or synthetic antibody claim 1 , or an antigen binding portion thereof claim 1 , that binds to the peptide of .24. A pharmaceutical composition comprising the peptide of and a pharmaceutically acceptable carrier.25. A pharmaceutical composition comprising the fusion protein of and a pharmaceutically acceptable carrier.26. A pharmaceutical composition comprising the conjugate of and a pharmaceutically acceptable carrier.2729-. (canceled)30. A pharmaceutical composition ...

LISTERIA-BASED IMMUNOGENIC COMPOSITIONS FOR ELICITING ANTI-TUMOR RESPONSES

The present invention is directed to compositions comprising an immune checkpoint inhibitor or a T cell stimulator or a combination thereof, and a live attenuated recombinant strain comprising a fusion polypeptide comprising a truncated Listeriolysin O protein, a truncated ActA protein, or a PEST amino acid sequence fused to a tumor-associated antigen. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor or a cancer, comprising the step of administering the same. 1Listeria. An immunogenic composition comprising (i) an immune checkpoint inhibitor and/or a T-cell stimulator , and (ii) a recombinant attenuated strain comprising a nucleic acid molecule , said nucleic acid molecule comprising a first open reading frame encoding a fusion polypeptide , wherein said fusion polypeptide comprises a truncated Listeriolysin O protein , a truncated ActA protein , or a PEST amino acid sequence fused to a heterologous antigen or fragment thereof.2. (canceled)3. (canceled)4Listeria. The composition of claim 1 , wherein said nucleic acid molecule is integrated into the genome.5Listeria. The composition of claim 1 , wherein said nucleic acid molecule is in a bacterial artificial chromosome in said recombinant strain.6Listeria. The composition of claim 1 , wherein said nucleic acid molecule is in a plasmid in said recombinant strain.7Listeria. The composition of claim 6 , wherein said plasmid is stably maintained in said recombinant strain in the absence of antibiotic selection.8Listeria.. The composition of claim 6 , wherein said plasmid does not confer antibiotic resistance upon said recombinant9. The composition of claim 1 , wherein said heterologous antigen is a tumor-associated antigen.10. The composition of claim 9 , wherein said tumor-associated antigen is a human papilloma virus (HPV).11. The composition of claim 9 , wherein said tumor-associated antigen is an angiogenic antigen.12. (canceled)13. ( ...

METHODS AND COMPOSITIONS FOR INCREASING A T-EFFECTOR CELL TO REGULATORY T CELL RATIO

The present invention is directed to methods for increasing T-cell effector cell to regulatory T cell ratio. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor, comprising the step of administering to a subject a recombinant strain, comprising a fusion peptide that comprises an LLO fragment and tumor-associated antigen. 1ListeriaListeria. A method of eliciting an anti-tumor T cell response in a subject having a tumor or cancer , comprising the step of administering to said subject a recombinant strain comprising a recombinant nucleic acid , said nucleic acid molecule comprising a first open reading frame encoding a recombinant polypeptide and a second open reading frame second open reading frame encoding a metabolic , wherein said recombinant polypeptide comprises a truncated LLO protein fused to a heterologous antigen or fragment thereof , wherein said comprises a mutation in the endogenous alanine racemase gene (dal) , D-amino acid transferase gene (dat) , and actA genes , and wherein said T-cell response comprises increasing a ratio of T effector cells to regulatory T cells (Tregs) , thereby eliciting an anti-tumor T cell response in said subject.2. The method of claim 1 , wherein said tumor-associated antigen is a human papilloma virus E7 antigen.3. The method of any one of - claim 1 , wherein said truncated LLO protein is an N-terminal LLO.4. The method of claim 2 , wherein said LLO is set forth in SEQ ID NO: 2.5. The method of any one of - claim 2 , wherein said heterologous antigen is a tumor-associated antigen.6. The method of any one of - claim 2 , wherein said tumor-associated antigen is an angiogenic antigen.7Listeria. The method of any one of - claim 2 , wherein said lacks antibiotic resistance genes.8Listeria.. The method of any one of - claim 2 , wherein said recombinant nucleic acid is in a plasmid in said9. The method of claim 8 , wherein said plasmid is an episomal plasmid.10 ...

Beta-mannosylceramide and stimulation of nkt cell anti-tumor immunity

β-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of α-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising β-mannosylceramide, as well as methods of treatment of tumors are also provided.

COMPOSITIONS COMPRISING NUCLEIC ACIDS ENCODING HIV-1 REVERSE TRANSCRIPTASE CTL EPITOPES

The present invention provides peptides and proteins for use in second generation HIV vaccines and as diagnostic tools in the treatment and control of HIV infection. The antiviral protection shown by compositions of the present invention has not been previously achieved with an HLA epitope-enhanced vaccine. These findings define a critical balance between MHC affinity and receptor crossreactivity required for effective epitope enhancement and also demonstrate construction and efficacy of such a component of a new generation vaccine. 1. A method for preventing or treating an HIV-1 infection comprising administering a dose of an immunostimulating peptide having an amino acid sequence X1LYQYMDDV (SEQ ID NO:1) , wherein X1 is any hydrophobic amino acid in an amount effective to induce an immune response capable of preventing HIV-1 infection or reducing HIV-1 viral load in a patient.2. The method of claim 1 , wherein the patient is a human.3. The method of claim 2 , wherein the patient is a primate. The present invention relates to the fields of immunology and genetics, particularly with regard to HIV infection and prevention of the same. The present invention provides peptides and proteins for use in second generation HIV vaccines and as diagnostic tools in the treatment and control of HW infection. The antiviral protection shown by compositions of the present invention has not been previously achieved with an HLA epitope-enhanced vaccine. These findings define a critical balance between MHC affinity and receptor crossreactivity required for effective epitope enhancement and also demonstrate construction and efficacy of such a component of a new generation vaccine.Protection by classical vaccines such as polio vaccine is mediated mostly by neutralizing antibodies, but such antibody-inducing vaccines have been ineffective against viruses causing chronic infection such as HIV or hepatitis C virus. Rather, in this case, T-cell immunity might be crucial as has been ...

Molecular nanotags

A molecular nanotag is disclosed that includes a core nanoparticle with a diameter of less than about 100 nm, with an optional shell surrounding the core, and an armor bound to the surface of the core nanoparticle, or if present, to the surface of the shell. The molecular nanotag also includes a functionalized end with a fixed number of binding sites that can selectively bind to a molecular targeting ligand. Any one of, or any combination of, the core, the shell and the armor contribute to fluorescence, light scattering and/or ligand binding properties of the molecular tag that are detectable by microscopy or in a devices that measures intensity or power of fluorescence and light scattering. The light scattering intensity or power of the assembled structure is detectable above the specific level of the reference noise of a device detecting the light scattering intensity or power, its fluorescence intensity or power has sufficient brightness for detection above the limit of detection for the instrument, and ligand specificity is conferred by the ligand binding component. Methods of biomarker and biosignature detection using the molecular tags are also disclosed.

Beta-mannosylceramide and stimulation of nkt cell anti-tumor immunity

β-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of α-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising β-mannosylceramide, as well as methods of treatment of tumors are also provided.

RECOMBINANT VACCINE VIRUSES EXPRESSING IL-15 AND METHODS OF USING THE SAME

The invention is directed to compositions capable of augmenting the immunogenicity of a vaccine. The composition, or adjuvant, is administered to a mammal in need thereof in sequential or concurrent combination with a vaccine antigen. In one preferred aspect, the adjuvant is provided in the form of a recombinant poxvirus vector, such as a vaccinia virus vector, which comprises a nucleic acid sequence encoding IL-15. 138-. (canceled)39. A method for generating an immune response in an animal comprising administering an attenuated or nonvirulent vaccine virus vector comprising a nucleic acid sequence encoding mammalian IL-15 and an expression unit comprising a plurality of antigen encoding sequences operably linked to a first expression control sequence to an animal in an amount effective to stimulate the immune response.40. A method for generating an immune response in an animal comprising administering a vaccine composition comprising a nucleic acid sequence encoding mammalian IL-15 and an expression unit comprising a plurality of antigen encoding sequences operably linked to a first expression control sequence , to an animal in an amount effective to stimulate the immune response.41. The method of or , wherein the immune response comprises one or more of: the production of memory CD8 T cells specific for the at least one antigen , the production of memory CD4 T cells specific for the at least one antigen , and the production of antibodies specific for the at least one antigen.42. The method of or , wherein at least some of the antibodies are neutralizing antibodies.4346.-. (canceled)47. The method of or , further comprising re-administering the nucleic acid encoding the antigen and nucleic acid encoding IL-15 after an interval of time , wherein the interval is at least about 6 months after the first administration.48. The method of or , comprising re-administering the antigen after an interval of time , wherein the interval is at least about 8 months after the ...

OPTICAL CONFIGURATION METHODS FOR SPECTRAL SCATTER FLOW CYTOMETRY

Apparatus include an illumination source configured to produce and direct a multi-wavelength illumination beam to a microfluidic target that can include nanotags, a detector configured to receive a multi-wavelength detection beam from the microfluidic target and to produce a detection signal, wherein the multi-wavelength detection beam comprises light that is elastically side-scattered by an interaction between the multi-wavelength illumination beam and the nanotags in the microfluidic target, and a processor configured to receive the detection signal and to determine the presence of the nanotags in the microfluidic target by comparing multiple wavelength side-scatter intensity characteristics of the detection signal with predetermined multi-wavelength elastic side-scatter intensity profiles of one or more nanotag types. Methods are also disclosed that determine the presence of different nanotags responsive to a multi-wavelength detection beam based on a detected signal and predetermined multi-wavelength elastic side-scatter intensity profiles for different nanotag types. 1. An apparatus , comprising:an illumination source configured to produce and direct a multi-wavelength illumination beam to a microfluidic target that can include nanotags;a detector configured to receive a multi-wavelength detection beam from the microfluidic target and to produce a detection signal, wherein the multi-wavelength detection beam comprises light that is elastically side-scattered by an interaction between the multi-wavelength illumination beam and the nanotags in the microfluidic target; anda processor configured to receive the detection signal and to determine the presence of the nanotags in the microfluidic target by comparing multiple wavelength side-scatter intensity characteristics of the detection signal with predetermined multi-wavelength elastic side-scatter intensity profiles of one or more nanotag types.2. (canceled)3. The apparatus of claim 1 , wherein the processor is ...

PURIFICATION AND LABELING OF EXTRACELLULAR VESICLES USING A MIXED MODE RESIN COMPOSITION

Disclosed is a method of purifying extracellular vesicles in a sample comprising extracellular vesicles and molecules that are not bound to the extracellular vesicles. The method includes (a) providing a mixed mode resin composition containing a first resin having pores with a pore size that traps unbound molecules by at least by a size exclusion mechanism, and a second resin containing at least one affinity ligand; (b) contacting the sample with the mixed mode resin composition to trap at least a portion of the unbound molecules; and (c) separating the sample from the mixed mode resin composition and obtaining a sample containing extracellular vesicles at a higher concentration than prior to step (b). Further disclosed is a method of labeling an extracellular vesicle with a fluorophore that labels proteins which includes the use of a mixed mode resin composition.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF HER2-EXPRESSING SOLID TUMORS

Recombinant adenoviruses expressing the extracellular (EC) and transmembrane (TM) domains of human HER2 (HER2ECTM) are described. The recombinant adenoviruses express a chimeric fiber protein having the adenovirus type 35 (Ad5) shaft and knob domains, which facilitates transduction of human dendritic cells by the recombinant HER2ECTM expressing adenovirus. Compositions that include dendritic cells transduced by the recombinant adenovirus and their use for treating HER-positive tumors is described. 1. A method of treating a HER2-positive cancer in a subject , comprising:preparing autologous dendritic cells by culturing monocytes obtained from the subject in culture medium comprising AB allogeneic plasma or autologous plasma;transducing the autologous dendritic cells with a recombinant adenovirus type 5 (Ad5) expressing the extracellular (EC) and transmembrane (TM) domains of human HER2 and an adenovirus type 35 (Ad35) fiber protein; andadministering to the subject a composition comprising the autologous dendritic cells transduced with the recombinant adenovirus in a pharmaceutically acceptable carrier.2. The method of claim 1 , wherein the fiber protein comprises the amino acid sequence of SEQ ID NO: 3.3. The method of claim 1 , wherein the composition further comprises an adjuvant.4. The method of claim 1 , wherein the HER2-positive cancer is a breast cancer claim 1 , ovarian cancer claim 1 , colorectal cancer claim 1 , prostate cancer claim 1 , renal cell cancer claim 1 , bladder cancer claim 1 , gastroesophageal cancer claim 1 , non-small cell lung cancer claim 1 , sarcoma or ependymoma.5. The method of claim 4 , wherein the cancer is metastatic.6. The method of claim 1 , further comprising administering a checkpoint inhibitor.7. The method of claim 6 , wherein the checkpoint inhibitor is an anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) agent claim 6 , an anti-programmed cell death protein 1 (PD-1) agent claim 6 , an anti-programmed death ligand 1 (PD- ...

METHODS TO PREVENT TUMOR RECURRENCE BY BLOCKADE OF TGF-β

Methods are provided herein to prevent a tumor recurrence in a subject, involving administering to the subject an agent that blocks the TGF-β signaling pathway. In one embodiment, the agent inhibits the immunosuppressive effects of TGF-β. Also provided is a method of enhancing an immune respond in a subject to inhibit recurrence of a tumor by administering an agent which blocks the TGF-β signaling pathway. A method of enhancing the activity of an immune cell to inhibit recurrence of a tumor by contacting a TGF-β receptor-expressing cell with an agent which blocks the TGF-β signaling pathway is also provided, as are methods of screening for an agent that inhibits or measurably reduces the recurrence of a tumor.

Method of producing immune response

The present invention discloses a process for enhancing antibody response to an antigen. A novel step in the process is the preparation of a conjugate of the antigen with an anti-immunoglobulin. The conjugate thus prepared is then administered to a host for in vivo effect or presented to T and B cells in a suitable culture system for in vitro response. The present invention by increasing immunogenicity makes it possible to produce antibodies against very low doses of antigens and otherwise weak or insufficient antigens or synthetic vaccines.

Immunogenic peptides and methods of use for treating and preventing cancer

Disclosed are immunogenic peptides, related fusion proteins, nucleic acids encoding the peptides or fusion proteins, conjugates, expression vectors, host cells, and antibodies. Also, disclosed are pharmaceutical compositions, vaccines for use in the treatment or prevention of cancer, e.g., alveolar rhabodomyosarcoma, methods of stimulating a T cell to kill a tumor cell, methods of stimulating CD4 + and CD8 + T cells, and methods of treating or preventing cancer are further provided herein.

Immunogenic peptides and methods of use for treating and preventing cancer

Disclosed are immunogenic peptides, related fusion proteins, nucleic acids encoding the peptides or fusion proteins, conjugates, expression vectors, host cells, and antibodies. Also, disclosed are pharmaceutical compositions, vaccines for use in the treatment or prevention of cancer, e.g., alveolar rhabodomyosarcoma, methods of stimulating a T cell to kill a tumor cell, methods of stimulating CD4 + and CD8 + T cells, and methods of treating or preventing cancer are further provided herein.

Immunogenic peptides and methods of use for treating and preventing cancer

Disclosed are immunogenic peptides, related fusion proteins, nucleic acids encoding the peptides or fusion proteins, conjugates, expression vectors, host cells, and antibodies. Also, disclosed are pharmaceutical compositions, vaccines for use in the treatment or prevention of cancer, e.g., alveolar rhabodomyosarcoma, methods of stimulating a T cell to kill a tumor cell, methods of stimulating CD4 + and CD8 + T cells, and methods of treating or preventing cancer are further provided herein.

Immunogenic peptides for the treatment of prostate and breast cancer

Immunogenic T-cell receptor gamma Alternate Reading Frame Protein (TARP) polypeptides are disclosed herein. These immunogenic TARP polypeptides include nine consecutive amino acids of the amino acid sequence set forth as SEQ ID NO: 9 and do not comprise amino acids 1-26 or amino acids 38-58 of SEQ ID NO: 1. Several specific, non-limiting examples of these polypeptides are set forth as SEQ ID NOs: 3-7. Nucleic acids encoding these polypeptides, and host cells transfected with these nucleic acids, are also disclosed. Methods of using these polypeptides, and polynucleotides encoding these polypeptides, for the treatment of breast and prostate cancer are also disclosed.

Composite synthetic peptide construct eliciting neutralizing antibodies and cytotoxic t lymphocytes against hiv

Peptide constructs comprised of multideterminant T helper peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52-73 % of HIV positive, flu positive patients (cluster peptides), were co-linearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB and also shown to contain a dominant CTL epitope. Cognate help for peptide 18 antibody was elicited following a single immunization in all strains of mice which had previously responded to a T cell epitope encompassed by the peptides. In two strains of mice, the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, much higher antibody titers for 90 % neutralization in the range of 1:1000 to 1:16,000 were achieved. Spleen cells from mice of three distinct MHC haplotypes sharing the Dd class I MHC molecule but with different class II molecules, immunized with the compound peptides, exhibited enhanced gp160-specific CTL activity.

Listeria-based immunogenic compositions for eliciting anti-tumor responses

The present invention is directed to compositions comprising an immune checkpoint inhibitor or a T cell stimulator or a combination thereof, and a live attenuated recombinant

Enhanced hiv-1 vaccines and methods for their use

ENHANCED HIV-1 VACCINES AND METHODS FOR THEIR USE ABSTRACT The present invention provides peptides and proteins for use in second generation HIV vaccines and as diagnostic tools in the treatment and control of HIV infection. The antiviral protection shown by compositions of the present invention has not been previously achieved with an HLA epitope-enhanced vaccine. These findings define a critical balance between MHC affinity and receptor crossreactivity required for effective epitope enhancement and also demonstrate construction and efficacy of such a component of a new generation vaccine.

Synergistic effect of tgf-beta blockade and immunogenic agents on tumors

Methods are provided herein for synergistically affecting tumor growth in a subject, involving the administration to the subject of an agent that blocks the TGF- .beta. signaling pathway in combination with an immunogenic agent. The agent that blocks the TGF-.beta. signaling pathway is believed to inhibit the immunosuppressive effects of TGF-.beta., while the immunogenic agent is believed to enhance an immune response. Surprisingly, the combination of such elements produces a synergistic effect. In one embodiment, the administration of the IDl 1.16 anti-TGF-.beta. antibody in combination with the human papilloma virus E7(49-57) peptide enhances tumor regression and tumor-specific CTL response in the subject. In another embodiment, the administration of the IDl 1.16 anti-TGF-.beta. antibody in combination with irradiated CT26 cells enhances tumor regression in the subject. The method of administering the combination of agents to the subject is more effective than the administration of each agent individually, or the sum of their individual effects.

.beta.-mannosylceramide and stimulation of nkt cell anti-tumor immunity

ß-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of a-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising ß-mannosylceramide, as well as methods of treatment of tumors are also provided.

METHODS TO PREVENT TUMOR RECURRENCE BY BLOCKADE OF TGF-β

Methods are provided herein to prevent a tumor recurrence in a subject, involving administering to the subject an agent that blocks the TGF-β signaling pathway. In one embodiment, the agent inhibits the immunosuppressive effects of TGF-β. Also provided is a method of enhancing an immune respond in a subject to inhibit recurrence of a tumor by administering an agent which blocks the TGF-β signaling pathway. A method of enhancing the activity of an immune cell to inhibit recurrence of a tumor by contacting a TGF-β receptor-expressing cell with an agent which blocks the TGF-β signaling pathway is also provided, as are methods of screening for an agent that inhibits or measurably reduces the recurrence of a tumor.

Immunostimulatory combinations of tlr3 ligands with tlr2 and tlr9 agonists and methods of use

Human papilloma virus immunoreative peptides

This invention provides immunogenic peptides from the HPV-18E6 protein that comprise class I restricted T cell epitopes and discloses methods of administering these peptides to individuals, and a method for monitoring or evaluating an immune response to HPV with these peptides.

Methods and compositions for increasing a T-effector cell to regulatory T cell ratio

The present invention is directed to methods for increasing T-cell effector cell to regulatory T cell ratio. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor, comprising the step of administering to a subject a recombinant

Recombinant vaccine viruses expressing IL-15 and methods using the same

The invention is directed to compositions capable of augmenting the immunogenicity of a vaccine. The composition, or adjuvant, is administered to a mammal in need thereof in sequential or concurrent combination with a vaccine antigen. In one preferred aspect, the adjuvant is provided in the form of a recombinant poxvirus vector, such as a vaccinia virus vector, which comprises a nucleic acid sequence encoding IL-15.

Recombinant vaccine viruses expressing il-15 and methods of using the same

The invention is directed to compositions capable of augmenting the immunogenicity of a vaccine. The composition, or adjuvant, is administered t o a mammal in need thereof in sequential or concurrent combination with a vaccine antigen. In one preferred aspect, the adjuvant is provided in the fo rm of a recombinant poxvirus vector, such as a vaccinia virus vector, which comprises a nucleic acid sequence encoding IL-15.

Method to predict antigenic sites recognized by t lymphocytes such as for design of vaccines

Method of predicting segments of protein sequences that are likely to be recognized by T lymphocytes and therefore to stimulate cellular immunity. The method involves determining the potential immunogenicity of certain protein sequences by using T-cell site predictors. These selected protein segments are evaluated and ranked according to the probability of the existence of a T-lymphocyte antigenic site. Peptides are thus selected as potential vaccine candidates in the treatment of infections for which T-cell mediated immunity is an important defense. Even when antibody immunity is the critical defense, helper T cells are necessary for a memory antibody response.

Composite synthetic peptide construct eliciting neutralizing antibodies and cytotoxic t lymphocytes against hiv

Peptide constructs comprised of multideterminant T helper peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52-73 % of HIV positive, flu positive patients (cluster peptides), were co-linearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB and also shown to contain a dominant CTL epitope. Cognate help for peptide 18 antibody was elicited following a single immunization in all strains of mice which had previously responded to a T cell epitope encompassed by the peptides. In two strains of mice, the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, much higher antibody titers for 90 % neutralization in the range of 1:1000 to 1:16,000 were achieved. Spleen cells from mice of three distinct MHC haplotypes sharing the Dd class I MHC molecule but with different class II molecules, immunized with the compound peptides, exhibited enhanced gp160-specific CTL activity.

Molecular nanotags

A molecular nanotag is disclosed that includes a core nanoparticle with a diameter of less than about 100 nm, with an optional shell surrounding the core, and an armor bound to the surface of the core nanoparticle, or if present, to the surface of the shell. The molecular nanotag also includes a functionalized end with a fixed number of binding sites that can selectively bind to a molecular targeting ligand. Any one of, or any combination of, the core, the shell and the armor contribute to fluorescence, light scattering and/or ligand binding properties of the molecular tag that are detectable by microscopy or in a devices that measures intensity or power of fluorescence and light scattering. The light scattering intensity or power of the assembled structure is detectable above the specific level of the reference noise of a device detecting the light scattering intensity or power, its fluorescence intensity or power has sufficient brightness for detection above the limit of detection for the instrument, and ligand specificity is conferred by the ligand binding component. Methods of biomarker and biosignature detection using the molecular tags are also disclosed.

Molecular nanotags

A molecular nanotag is disclosed that includes a core nanoparticle with a diameter of less than about 100 nm, with an optional shell surrounding the core, and an armor bound to the surface of the core nanoparticle, or if present, to the surface of the shell. The molecular nanotag also includes a functionalized end with a fixed number of binding sites that can selectively bind to a molecular targeting ligand. Any one of, or any combination of, the core, the shell and the armor contribute to fluorescence, light scattering and/or ligand binding properties of the molecular tag that are detectable by microscopy or in a devices that measures intensity or power of fluorescence and light scattering. The light scattering intensity or power of the assembled structure is detectable above the specific level of the reference noise of a device detecting the light scattering intensity or power, its fluorescence intensity or power has sufficient brightness for detection above the limit of detection for the instrument, and ligand specificity is conferred by the ligand binding component. Methods of biomarker and biosignature detection using the molecular tags are also disclosed.

Peptide for stimulation of cytotoxic t lymphocytes specific for hepatitis c virus

The cytotoxic T cell response to the protein encoded by the NS5 region of hepatitis C virus was determined using 28 peptides from NS5 which were selected by an amphipathicity algorithm as candidates for T cell epitopes. In BALB/c mice, a single relatively conserved epitope represented by a 16-residue synthetic peptide was presented by D d class I major histocompatibility complex (MHC) molecules to conventional CD4-CD8 + CTL. An exemplary peptide, which represents amino acid residues 2422-2437 of the polyprotein of the Chiron HCVI isolate, had the amino acid sequence MSYSWTGALVTPCAAE {SEQ ID NO: 1}. A CTL line specific for this peptide recognized the two known natural variants of this NS5 sequence, each with conservative substitutions. Thus, CTL can recognize the product of the HCV NS5 gene, the probable RNA polymerase, in association with class I MHC molecules on model target cells and may recognize the same epitope on hepatocytes or any other cells infected with the virus.

Multideterminant peptide antigens that stimulate helper t lymphocyte response to hiv in a range of human subjects

This invention relates to the selection and preparation of synthetic peptides which stimulate helper T lymphocyte response to HIV in a wide range of human subjects. These multideterminant peptides are, therefore, useful for the production of vaccines against HIV infection and for diagnostic procedures to test for HIV seroconversion.

Multi-epitope tarp peptide vaccine and uses thereof

The present disclosure describes immunogenic T cell receptor γ alternate reading frame protein (TARP) peptide compositions that include multiple epitopes of the TARP protein. The disclosed compositions can be used for the treatment of TARP-expressing cancers, such as prostate cancer, breast cancer and mesothelioma. In some embodiments, the TARP peptide compositions disclosed herein include sets of overlapping TARP peptides that each have a length of about 15 to about 25 amino acids, and comprise about 5 to about 15 amino acids that are identical to at least another overlapping peptide in the set. In particular examples, the combination of the overlapping TARP peptides in the set encompasses the complete amino acid sequence of human TARP. The multi-epitope peptide compositions described herein include both CD4 and CD8 epitopes, a feature that is important for eliciting CD4 + T cell and CD8 + T cell, as well as humoral immune responses.

SYNTHETIC COMPOUND PEPTIDE CONSTRUCT WHICH CAUSES NEUTRALIZING ANTIBODIES AND CYTOTOXIC T-LYMPHOCYTES AGAINST HIV.

CONSTRUCCIONES PEPTIDAS QUE INCLUYEN PEPTIDOS AYUDANTES DEL MULTIDETERMINANTE T DE LA GLICOPROTEINA ENVUELTA DE VIH PREVIAMENTE IDENTIFICADA PARA INDUCIR RESPUESTAS PROLIFERATIVAS EN CUATRO HAPLOTIPOS DIFERENTES DE RATAS Y RESPUESTAS IL-2 EN EL 52-73% DE LOS VIH POSITIVOS; PACIENTES CON GRIPE (PEPTIDOS AGLOMERANTES) FUERON SINTETIZADOS COLINEALMENTE CON EL PEPTIDO 18 DEL ANILLO V3 DE VIH-1 GP 160, CORRESPONDIENTE AL DETERMINANTE NEUTRALIZADOR PRINCIPAL DE VIH-IIIB Y QUE TAMBIEN DEMUESTRAN CONTENER UN EPITOPO CTL. LA AYUDA ANALOGA PARA EL ANTICUERPO DE PEPTIDO 18 FUE INCITADA SIGUIENDO UNA SOLA INMUNIZACION EN TODOS LAS RAMAS DE RATAS QUE HABIAN RESPONDIDO PREVIAMENTE AL EPITOPO DE CELULA T INCLUIDO POR LOS PEPTIDOS. EN DOS RAMAS DE RATAS, EL NIVEL DE ANTICUERPO NEUTRALIZADOR CONSEGUIDO FUE COMPARABLE A LOS NIVELES ADECUADOS PARA LA PROTECCION DE RETOS VIRALES HOMOLOGOS EN CHIMPACES. DESPUES DE UN SOLO CHOQUE, SE CONSIGUIERON ANTICUERPOS MUCHO MAS ELEVADOS QUE RONDARON EL 90% DE NEUTRALIZACION EN EL INTERVALO DE 1:1000 A 1:16000. CELULAS DE BAZO DE LAS RATAS DE 3 HAPLOTIPOS NHC DIFERENCIADOS QUE COMPARTEN EL D{SUP,D} DE CLASE I DE LA MOLECULA NHC PERO CON DIFERENTES MOLECULAS DE CLASE II, INMUNIZADAS CON LOS PEPTIDOS DEL COMPUESTO, EXHIBIERON UNA ACTIVIDAD CTL GP 160-ESPECIFICA REFORZADA. PEPTIDE CONSTRUCTIONS INCLUDING MULTIDETERMINANT T ASSISTANT PEPTIDES OF GLYCOPROTEIN INVOLVED FROM HIV PREVIOUSLY IDENTIFIED TO INDUCE PROLIFERATIVE RESPONSES IN FOUR DIFFERENT RATINGS AND ILL-2 RESPONSES IN 52 FLU PATIENTS (BINDING PEPTIDES) WERE SYNTHESIZED COLLINALLY WITH PEPTIDE 18 OF HIV-1 GP 160 RING V3, CORRESPONDING TO THE DETERMINING MAIN NEUTRALIZER OF HIV-IIIB AND ALSO DEMONSTRATED CONTAINING AN EPIT. ANALOG AID FOR PEPTIDO 18 ANTIBODY WAS INITIATED FOLLOWING A SINGLE IMMUNIZATION IN ALL RAT BRANCHES THAT HAD PREVIOUSLY RESPONDED TO THE CELL EPITOPE INCLUDED BY THE PEPTIDES. IN TWO RAT BRANCHES, THE LEVEL OF NEUTRALIZING ANTIBODY ACHIEVED WAS COMPARABLE TO THE LEVELS ...

Synthetic vaccine against aids virus

Immunostimulatory combinations of tlr ligands and methods of use

The present invention provides immunostimulatory combinations of TLR ligands and therapeutic and/or prophylactic methods that include administering an immunostimulatory combination to a subject. In general, the immunostimulatory combinations described herein can provide an increased immune response compared to other immunostimulatory combinations and/or compositions.

β-mannosylceramide and stimulation of NKT cell anti-tumor immunity

β-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of α-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising β-mannosylceramide, as well as methods of treatment of tumors are also provided.

Peptides stimulating cytotoxic t cells immune to hiv rt

An epitope in the human immunodeficiency virus-1 (HIV-1) reverse transcriptase that is conserved among HIV strains and that is recognized by both murine and human cytotoxic T cells has been identified. Peptides that are derived from this epitope and that are capable of eliciting cytotoxic T cells that kill cells that express reverse transcriptase are provided. Test kits and meth-ods for identifying HIV-infected individuals using the peptides are also provided. The optimal antigenic side of the HIV-1 reverse transcriptase, which was identified using a murine antigen-specific CD8 + Class I MHC-molecule-restricted cytotoxic T-cell line, includes residues 203-219. This peptide was recognized by cytotoxic lymphocytes from HIV seropositive individuals, but not by cytotoxic lymphocytes from seronegative individuals, and, thus provide a means for diagnosing HIV infection. Test kits and methods for identifying HIV-infected individuals using the peptides are provided. Peptides that include this antigenic site provide a means for producing an immunologic response against a broad range of HIV, and, therefore may be useful for inclusion in an AIDS vaccine. Compositions that contain these peptides and that are formulated for parenteral administration are provided.

Molecular nanotags

A molecular nanotag is disclosed that includes a core nanoparticle with a diameter of less than about 100 nm, with an optional shell surrounding the core, and an armor bound to the surface of the core nanoparticle, or if present, to the surface of the shell. The molecular nanotag also includes a functionalized end with a fixed number of binding sites that can selectively bind to a molecular targeting ligand. Any one of, or any combination of, the core, the shell and the armor contribute to fluorescence, light scattering and/or ligand binding properties of the molecular tag that are detectable by microscopy or in a devices that measures intensity or power of fluorescence and light scattering. The light scattering intensity or power of the assembled structure is detectable above the specific level of the reference noise of a device detecting the light scattering intensity or power, its fluorescence intensity or power has sufficient brightness for detection above the limit of detection for the instrument, and ligand specificity is conferred by the ligand binding component. Methods of biomarker and biosignature detection using the molecular tags are also disclosed.

Biomarker analysis for high-throughput diagnostic multiplex data

Flow cytometry of extracellular vesicle (EV) samples produces counts associated with channels defined by combinations of capture agents and detection agents, typically capture antibodies and detection antibodies having associated markers such as fluorophores. Sample groupings are obtained by processing channel counts using principal component analysis or other techniques. Identification of a particular sample grouping permits selection of associated channels for detection of samples exhibiting characteristics of the particular sample grouping.

Human papilloma virus immunoreactive peptides

This invention provides immunogenic peptides from the HPV-18E6 protein that comprise class I restricted T cell epitopes and discloses methods of administering these peptides to individuals, and a method for monitoring or evaluating an immune response to HPV with these peptides.

MULTIEPITOP-TARP-PEPTID VACCINE AND APPLICATIONS THEREOF.

MUCOSALE CYTOTOXIC T-LYMPHOCYTE RESPONSE

Synthetic peptides which induce cellular immunity to the aids virus and aids viral proteins

Compositions and methods for the treatment of HER2-expressing solid tumors

Recombinant adenoviruses expressing the extracellular (EC) and transmembrane (TM) domains of human HER2 (HER2ECTM) are described. The recombinant adenoviruses express a chimeric fiber protein having the adenovirus type 35 (Ad5) shaft and knob domains, which facilitates transduction of human dendritic cells by the recombinant HER2ECTM expressing adenovirus. Compositions that include dendritic cells transduced by the recombinant adenovirus and their use for treating HER-positive tumors is described.

Multideterminant peptide antigens that stimulate helper t lymphocyte response to hiv in a range of human subjects

This invention relates to the selection and preparation of synthetic peptides which stimulate helper T lymphocyte response to HIV in a wide range of human subjects. These multideterminant peptides are, therefore, useful for the production of vaccines against HIV infection and for diagnostic procedures to test for HIV seroconversion.

Multideterminant peptides eliciting helper T-lymphocyte, cytotoxic T-lymphocyte, and neutralizing antibody responses against HIV-1

This invention is directed toward a multideterminant human immunodeficiency virus type 1 (HIV-1) peptide which comprises a covalently linked T-helper (Th) lymphocyte epitope, cytotoxic T-lymphocyte (CTL) epitope, and an epitope capable of eliciting a neutralizing antibody response (AbN), wherein said peptide has the following amino acid sequence: KQIINMWQEVGKAMYAPPISGQIRRIHIGPGRAFYTTKN. This peptide has the further characteristic of evoking all three of these immune responses in hosts having a broad range of major histocompatibility complex (MHC) types. This peptide is useful as an immunogen to generate broad immune responses in a host, to assess immune responses in virally infected hosts, and as a diagnostic reagent to detect viral infection.

Optical configuration methods for spectral scatter flow cytometry

Apparatus include an illumination source configured to produce and direct a multi-wavelength illumination beam to a microfluidic target that can include nanotags, a detector configured to receive a multi-wavelength detection beam from the microfluidic target and to produce a detection signal, wherein the multi-wavelength detection beam comprises light that is elastically side-scattered by an interaction between the multi-wavelength illumination beam and the nanotags in the microfluidic target, and a processor configured to receive the detection signal and to determine the presence of the nanotags in the microfluidic target by comparing multiple wavelength side-scatter intensity characteristics of the detection signal with predetermined multi-wavelength elastic side-scatter intensity profiles of one or more nanotag types. Methods are also disclosed that determine the presence of different nanotags responsive to a multi-wavelength detection beam based on a detected signal and predetermined multi-wavelength elastic side-scatter intensity profiles for different nanotag types.

Compositions and methods for the treatment of her2-expressing solid tumors

Recombinant adenoviruses expressing the extracellular (EC) and transmembrane (TM) domains of human HER2 (HER2ECTM) are described. The recombinant adenoviruses express a chimeric fiber protein having the adenovirus type 35 (Ad5) shaft and knob domains, which facilitates transduction of human dendritic cells by the recombinant HER2ECTM expressing adenovirus. Compositions that include dendritic cells transduced by the recombinant adenovirus and their use for treating HER-positive tumors is described.

Synergistic Effect of Tgf-Beta Blockade and Immunogenic Agents on Tumors

Methods are provided herein for synergistically affecting tumor growth in a subject, involving the administration to the subject of an agent that blocks the TGF-β signaling pathway in combination with an immunogenic agent. The agent that blocks the TGF-β signaling pathway is believed to inhibit the immunosuppressive effects of TGF-β, while the immunogenic agent is believed to enhance an immune response. Surprisingly, the combination of such elements produces a synergistic effect. In one embodiment, the administration of the 1D11.16 anti-TGF-β antibody in combination with the human papilloma virus E7 (49-57) peptide enhances tumor regression and tumor-specific CTL response in the subject. In another embodiment, the administration of the 1D11.16 anti-TGF-β antibody in combination with irradiated CT26 cells enhances tumor regression in the subject. The method of administering the combination of agents to the subject is more effective than the administration of each agent individually, or the sum of their individual effects.

Immunogenic peptides fragments of xage-1

XAGE-1 is a gene expressed in a number of important human cancers, including prostate cancer, lung cancer, breast cancer, ovarian cancer, glioblastoma, pancreatic cancer, and melanoma. It has now been discovered that peptides of fifty or fewer amino acids comprising the sequence X1X2X3PSAPSPX4 (SEQ ID NO:5), where X1 is any amino acid and is preferably G or Y; X2 is selected from the group consisting of L, M, A, I, V, and T, with L and M being preferred; X3 is a hydrophobic residue, M or A; and X4 is V, M, L, A, I, or T, and is preferably V, bind to the HLA-A2 MHC class I molecule, and can be used to raise immune responses to XAGE-1-expressing cancers. In some embodiments, the P at position 7, the S at position 8, or the P at position 9, can be omitted to create a 9 amino acid peptide. The invention provides immunogenic peptides, nucleic acids encoding them, vectors comprising the nucleic acids, uses of the peptides and nucleic acids for manufacture of medicaments, methods of using the peptides and nucleic acids, and compositions of the peptides or nucleic acids in pharmaceutically acceptable carriers.

Immunogenic peptides and methods of use for treating and preventing cancer

Disclosed are immunogenic peptides, related fusion proteins, nucleic acids encoding the peptides or fusion proteins, conjugates, expression vectors, host cells, and antibodies. Also, disclosed are pharmaceutical compositions, vaccines for use in the treatment or prevention of cancer, e.g., alveolar rhabodomyosarcoma, methods of stimulating a T cell to kill a tumor cell, methods of stimulating CD4 + and CD8 + T cells, and methods of treating or preventing cancer are further provided herein.

Methods to prevent tumor recurrence by blockade of TGF-Beta

Methods are provided herein to prevent a tumor recurrence in a subject, involving administering to the subject an agent that blocks the TGF-beta signaling pathway. In one embodiment, the agent inhibits the immunosuppressive effects of TGF-beta. Also provided is a method of enhancing an immune respond in a subject to inhibit recurrence of a tumor by administering an agent which blocks the TGF-beta signaling pathway. A method of enhancing the activity of an immune cell to inhibit recurrence of a tumor by contacting a TGF-beta receptor-expressing cell with an agent which blocks the TGF-beta signaling pathway is also provided, as are methods of screening for an agent that inhibits or measurably reduces the recurrence of a tumor.

Mucosal cytotoxic t lymphocyte responses

The invention provides methods for induction of an antigen-specific, mucosal cytotoxic T lymphocyte response useful in preventing and treating infections with pathogens that gain entry via a mucosal surface.

Molecular nanotags

A molecular nanotag is disclosed that includes a core nanoparticle with a diameter of less than about 100 nm, with an optional shell surrounding the core, and an armor bound to the surface of the core nanoparticle, or if present, to the surface of the shell. The molecular nanotag also includes a functionalized end with a fixed number of binding sites that can selectively bind to a molecular targeting ligand. Any one of, or any combination of, the core, the shell and the armor contribute to fluorescence, light scattering and/or ligand binding properties of the molecular tag that are detectable by microscopy or in a devices that measures intensity or power of fluorescence and light scattering. Methods of biomarker and biosignature detection using the molecular tags are also disclosed.

Peptid für die stimulierung von für hepatitis c virus spesifischen cytotoischen t lymphozyten

Mukosale zytotoxische t-lymphozytenantwort

Modifizierte hcv peptid-impfstoffe

Biomarker analysis for high-throughput diagnostic multiplex data

Modified hcv peptide vaccines

The present invention provides 1) an isolated peptide having the amino acid sequence DLMGYIPAV, (SEQ ID NO: 1); 2) an isolated HCV core polypeptide comprising an L→A substitution at amino acid position 139; 3) an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2; and 4) a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence SEQ ID NO: 1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. The present invention further provides methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.

Biomarkøranalyse for diagnostiske multiplexdata med højt gennemløb

Synthetisches antigen zum bewirken einer anti-hiv-reaktion

Adjuvanted mucosal subunit vaccines for preventing sars-cov-2 transmission and infection

Immunogenic compositions that include SARS-CoV-2 spike (S) protein, S1 protein, or S2 protein, and an adjuvant, such as alum, or a combination of CpG oligodeoxynucleotide, Poly I:C, and IL-15, and nanoparticle compositions that include SARS-CoV-2 S protein, S1 protein, or S2 protein, and CpG oligonucleotide, poly(I:C), and IL-15, are provided. Also provided are methods of using such compositions, for example a prime intramuscular administration followed by one or more intranasal boosters that include the disclosed nanoparticles, to generate an immune response to SARS-CoV-2 in a subject, for example respiratory mucosal immunity, for example to prevent SARS-CoV-2 infection or transmission to other subjects.

Method and composition for inhibition of tumor growth and enhancing an immune response

Provided is a method and composition for enhancing an immune response in a subject by administering to the subject an inhibitor of IL-13 or an inhibitor of an NK-T cell to the subject. The method can be used to prevent growth of a tumor in the subject, e.g., to inhibit tumor recurrence or metastasis. The method can also be used to enhance a response to a vaccine in a subject.

Method and composition for inhibition of tumor growth and enhancing an immune response

Provided is a method and composition for enhancing an immune response in a subject by administering to the subject an inhibitor of IL-13 or an inhibitor of an NK-T cell to the subject. The method can be used to prevent growth of a tumor in the subject, e.g., to inhibit tumor recurrence or metastasis. The method can also be used to enhance a response to a vaccine in a subject.

Method and composition for inhibition of tumor growth and enhancing an immune response

Provided is a method and composition for enhancing an immune response in a subject by administering to the subject an inhibitor of IL-13 or an inhibitor of an NK-T cell to the subject. The method can be used to prevent growth of a tumor in the subject, e.g., to inhibit tumor recurrence or metastasis. The method can also be used to enhance a response to a vaccine in a subject.

Adjuvanted mucosal subunit vaccines for preventing sars-cov-2 transmission and infection

Immunogenic compositions that include SARS-CoV-2 spike (S) protein, S1 protein, or S2 protein, and an adjuvant, such as alum, or a combination of CpG oligodeoxynucleotide, Poly I:C, and IL-15, and nanoparticle compositions that include SARS-CoV-2 S protein, S1 protein, or S2 protein, and CpG oligonucleotide, poly(I:C), and IL-15, are provided. Also provided are methods of using such compositions, for example a prime intramuscular administration followed by one or more intranasal boosters that include the disclosed nanoparticles, to generate an immune response to SARS-CoV-2 in a subject, for example respiratory mucosal immunity, for example to prevent SARS-CoV-2 infection or transmission to other subjects.

Modified hcv peptide vaccines

The present invention provides 1) an isolated peptide having the amino acid sequence DLMGYIPAV, (SEQ ID NO: 1); 2) an isolated HCV core polypeptide comprising an L→A substitution at amino acid position 139; 3) an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2; and 4) a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence SEQ ID NO: 1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. The present invention further provides methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.

Peptid aus dem inneren des hepatitis-c-virus brauchbar für die stimulation cytotoxischer t- lymphocyten und die diagnose des hcv-kontaktes

Análisis de biomarcadores para datos multiplex de diagnóstico de alto rendimiento

Purification and labeling of extracellular vesicles using a mixed mode resin composition

Disclosed is a method of purifying extracellular vesicles in a sample comprising extracellular vesicles and molecules that are not bound to the extracellular vesicles. The method includes (a) providing a mixed mode resin composition containing a first resin having pores with a pore size that traps unbound molecules by at least by a size exclusion mechanism, and a second resin containing at least one affinity ligand; (b) contacting the sample with the mixed mode resin composition to trap at least a portion of the unbound molecules; and (c) separating the sample from the mixed mode resin composition and obtaining a sample containing extracellular vesicles at a higher concentration than prior to step (b). Further disclosed is a method of labeling an extracellular vesicle with a fluorophore that labels proteins which includes the use of a mixed mode resin composition.

Hepatitis c virus core peptide for stimulation of cytotoxic t lymphocytes and diagnosis of hcv exposure

Peptides representing portions of the Hepatitis C Virus core protein that represent cytotoxic T lymphocyte epitopes are disclosed. The peptides also have amino acid sequences corresponding to binding motifs for human HLA molecules. The peptides are useful as vaccines for the prevention or treatment of Hepatitis C Virus infection and can also be used as reagents for diagnostic tests for Hepatitis C Virus exposure or for prognostic tests for predicting the clinical course of Hepatitis C Virus infection.

Optical configuration methods for spectral scatter flow cytometry

Apparatus include an illumination source configured to produce and direct a multi-wavelength illumination beam to a microfluidic target that can include nanotags, a detector configured to receive a multi-wavelength detection beam from the microfluidic target and to produce a detection signal, wherein the multi-wavelength detection beam comprises light that is elastically side-scattered by an interaction between the multi-wavelength illumination beam and the nanotags in the microfluidic target, and a processor configured to receive the detection signal and to determine the presence of the nanotags in the microfluidic target by comparing multiple wavelength side-scatter intensity characteristics of the detection signal with predetermined multi-wavelength elastic side-scatter intensity profiles of one or more nanotag types. Methods are also disclosed that determine the presence of different nanotags responsive to a multi-wavelength detection beam based on a detected signal and predetermined multi-wavelength elastic side-scatter intensity profiles for different nanotag types.

Künstlicher impfstoff gegen aids-virus

Synthetische mischpeptide, die die entstehung von neutralisierenden antikörpern und die wirkung der cytotoxischen t-lymphozyten gegen hiv hervorufen

Peptid-antigene bestehend aus multi- determinanten, die die t-helfer lymphozyten- antwort gegen hiv in einem weiten bereich von betroffenen menschen stimulieren

Immunotherapeutic methods using tumor antigenic peptides coated on cells and vaccines made thereof

Vaccines and methods for prevention and treatment of drug-resistant hiv-1 and hepatitis b virus

The present invention provides methods for lowering a viral load of a virus resistant to an antiviral drug by inducing cytotoxic T lymphocytes (CTL) to recognize a predetermined mutated epitope within a viral protein of the drug-resistant virus. CTLs are induced by immunizing a host with a peptide comprising the predetermined mutation. The immunostimulating peptide may be further improved by epitope-enhancement for inducing specific CTLs. The antiviral protection against drug-resistant virus shown by compositions of the present invention and mediated by human HLA-restricted CTL has not been previously achieved.