Vaccine compositions for treatment of Zika virus

The present disclosure provides compositions and methods useful for preventing and treating Zika virus infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more Zika epitopes, such as, for example, from Zika envelope glycoprotein E and the Zika structural protein NS1 including variants thereof.

Selective differentiation, identification, and modulation of human TH17 cells

The embodiments provide for the modulation of both the differentiation and activity of human T H 17 cells. More specifically, human T H 17 cell differentiation can modulated by TGF-β and IL-21, and their agonists and antagonists. Function of T H 17 cells can be modulated by, for example, BLT1 or podoplanin, and their agonists and antagonists. Additionally, the embodiments provide for the identification of T H 17 cells. More specifically, human T H 17 cells specifically upregulate BLT1 and podoplanin.

Compositions and methods for treatment of cytomegalovirus

The present disclosure provides compositions and methods useful for treating HCMV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCMV epitopes, such as, for example, from HCMV envelope glycoproteins gB and/or gH and/or tegument protein pp65. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation).

Methods for preparing vesicles and formulations produced therefrom

The present disclosure provides methods for preparing vesicles. In some embodiments, the methods involve providing a molten mixture of vesicle forming lipids and then adding the molten mixture to an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. In other embodiments, the methods involve providing a lyophilized lipid product and rehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. The lyophilized lipid product is prepared by melting vesicle-forming lipids to produce a molten lipid mixture and then lyophilizing the molten lipid mixture. The present disclosure also provides antigen-containing vesicle formulations prepared using these methods. The present disclosure also provides kits that include a lyophilized lipid product in a first container and an aqueous solution comprising an antigen in a second container.

Compositions and methods for treating influenza

The present disclosure provides compositions and methods useful for treating influenza. As described herein, provided compositions and methods are based on the development of certain compositions that include an influenza virus hemagglutinin antigen in combination with lipid vesicles that include a non-ionic surfactant (NISVs) and optionally an adjuvant. In certain embodiments, provided compositions remain potent even when they are not stored in a standard cold-chain system (i.e., they are thermostable).

Systems and Methods for Oil and gas Recovery

The present inventions are related to oil and gas recovery, and in particular to enhanced oil and gas separation during oil and gas recovery. 1. A oil recovery system , the system comprising:a separator device operable to receive an input fluid and to separate the input fluid into a gas portion and an emulsion portion;a compression pump operable to receive a part of the emulsion portion and to increase the pressure from a first pressure to a second pressure to yield a high pressure fluid;and a pressure reduction system operable to reduce the pressure of a prepared input to a third pressure to yield a return product, wherein the pressure reduction system flows the return product back into the separator device, and wherein the prepared input is derived from the high pressure fluid.2. The oil recovery system of claim 1 , wherein the first pressure is approximately the pressure in the separator device.3. The oil recovery system of claim 1 , wherein both the first pressure and the third pressure are approximately equal to the pressure in the separator device.4. The oil recovery system of claim 1 , wherein the second pressure is at least five times greater than the first pressure.5. The oil recovery system of claim 1 , wherein the first pressure is less than one hundred psi claim 1 , and the second pressure is greater than five hundred psi.6. The oil recovery system of claim 1 , wherein the gas portion is a first gas portion claim 1 , the part of the emulsion portion is a first part of the emulsion portion claim 1 , and wherein the system further comprises:a treater device operable to receive a second part of the emulsion portion and to separate the emulsion portion into a second gas portion, an oil portion, and a water portion; andwherein the pump is further operable to receive a part of the oil portion mixed with the first part of the emulsion portion and to increase the pressure from the first pressure to the second pressure to yield the high pressure fluid.7. The oil ...

Methods for preparing vesicles and formulations produced therefrom

The present disclosure provides methods for preparing vesicles. In general, these methods include steps of providing a lyophilized lipid product and rehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. The lyophilized lipid product is prepared by dissolving vesicle-forming lipids in a polar-protic water-miscible organic solvent to produce a lipid solution and then lyophilizing the lipid solution. The present disclosure also provides antigen-containing vesicle formulations prepared using these methods. The present disclosure also provides kits that include a lyophilized lipid product in a first container and an aqueous solution comprising an antigen in a second container.

Compositions and methods for treating influenza

The present disclosure provides compositions and methods useful for treating influenza. As described herein, provided compositions and methods are based on the development of certain compositions that include an influenza virus hemagglutinin antigen in combination with lipid vesicles that include a non-ionic surfactant (NISVs) and optionally an adjuvant. In certain embodiments, provided compositions remain potent even when they are not stored in a standard cold-chain system (i.e., they are thermostable).

Compositions and methods for treating influenza

The present application provides compositions and methods useful for treating influenza. As described herein, the compositions and methods are based on the development of peptides and peptide combinations which exhibit immunogenic properties against influenza. In some embodiments, the peptide combinations induce a protective response against multiple strains of influenza, e.g., seasonal strains of influenza or even the new pandemic influenza A (H1N1) virus of swine origin.

Methods for preparing vesicles and formulations produced therefrom

The present disclosure provides methods for preparing vesicles. In some embodiments, the methods involve providing a molten mixture of vesicle forming lipids and then adding the molten mixture to an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. In other embodiments, the methods involve providing a lyophilized lipid product and rehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. The lyophilized lipid product is prepared by melting vesicle-forming lipids to produce a molten lipid mixture and then lyophilizing the molten lipid mixture. The present disclosure also provides antigen-containing vesicle formulations prepared using these methods. The present disclosure also provides kits that include a lyophilized lipid product in a first container and an aqueous solution comprising an antigen in a second container.

METHODS FOR PREPARING VESICLES AND FORMULATIONS PRODUCED THEREFROM

The present disclosure provides methods for preparing vesicles. In general, these methods include steps of providing a lyophilized lipid product and rehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. The lyophilized lipid product is prepared by dissolving vesicle-forming lipids in a polar-protic water-miscible organic solvent to produce a lipid solution and then lyophilizing the lipid solution. The present disclosure also provides antigen-containing vesicle formulations prepared using these methods. The present disclosure also provides kits that include a lyophilized lipid product in a first container and an aqueous solution comprising an antigen in a second container. 1. A method comprising:providing a lyophilized lipid product that was prepared by dissolving vesicle-forming lipids in a polar-protic water-miscible organic solvent to produce a lipid solution and then lyophilizing the lipid solution to produce the lyophilized lipid product; andrehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen-containing vesicles are formed.2. The method of further comprising preparing the lyophilized lipid product by:dissolving vesicle-forming lipids in a polar-protic water-miscible organic solvent to produce a lipid solution; andlyophilizing the lipid solution to produce the lyophilized lipid product.35-. (canceled)6. The method of claim 1 , wherein the vesicle-forming lipids comprise a phospholipid.7. The method of claim 1 , wherein the vesicle-forming lipids comprise a non-ionic surfactant.89-. (canceled)10. The method of claim 7 , wherein the non-ionic surfactant is 1-monopalmitoyl glycerol.11. (canceled)12. The method of claim 1 , wherein the polar-protic water-miscible organic solvent is an aliphatic alcohol having 3-5 carbon atoms.13. The method of claim 1 , wherein the polar-protic water-miscible organic solvent is an aliphatic ...

COMPOSITIONS AND METHODS FOR TREATING INFLUENZA

The present disclosure provides compositions and methods useful for treating influenza. As described herein, provided compositions and methods are based on the development of certain compositions that include an influenza virus hemagglutinin antigen in combination with lipid vesicles that include a non-ionic surfactant (NISVs) and optionally an adjuvant. In certain embodiments, provided compositions remain potent even when they are not stored in a standard cold-chain system (i.e., they are thermostable). 1. A composition comprising an influenza virus hemagglutinin antigen and lipid vesicles , wherein the lipid vesicles are comprised of lipids that are present in the composition in an amount that achieves a lipid:antigen weight ratio within a range of about 50:1 to about 400:1 and the lipids include a non-ionic surfactant.2. The composition of claim 1 , wherein the composition is immunogenic.3. An immunogenic composition comprising an influenza virus hemagglutinin antigen and lipid vesicles claim 1 , wherein the lipid vesicles are comprised of lipids that are present in the composition in an amount that achieves a lipid:antigen weight ratio of at least about 50:1 and the lipids include a non-ionic surfactant.43. The composition of any one of - claims 1 , wherein the composition is a liquid.53. The composition of any one of - claims 1 , wherein the composition is dried.6. A dried composition comprising an influenza virus hemagglutinin antigen and lipid vesicles claims 1 , wherein the lipid vesicles are comprised of lipids that are present in the composition in an amount that achieves a lipid:antigen weight ratio of at least about 30:1 claims 1 , the lipids include a non-ionic surfactant and the moisture content of the composition is less than about 2% by weight.76. The composition of any one of - claims 1 , wherein the lipid:antigen weight ratio is at least about 100:1.86. The composition of any one of - claims 1 , wherein the lipid:antigen weight ratio is at least ...

COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTIONS

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an attenuated or inactivated virus in combination with a non-ionic surfactant vesicle (NISV).

METHODS FOR PREPARING VESICLES AND FORMULATIONS PRODUCED THEREFROM

The present disclosure provides methods for preparing vesicles. In one aspect, the methods involve providing a molten mixture of vesicle-forming lipids and adding the molten mixture of vesicle-forming lipids to an aqueous solution comprising an antigen such that antigen-containing vesicles are formed, wherein in the step of adding the molten mixture of vesicle forming lipids is at a temperature of less than 120° C. In another aspect, the methods involve providing a molten mixture of vesicle-forming lipids and adding an aqueous solution comprising an antigen to the molten mixture of vesicle-forming lipids such that antigen-containing vesicles are formed, wherein the resulting mixture is placed under temperature-controlled conditions of less than 60° C. In yet another aspect, the methods involve providing a solution of vesicle forming lipids and adding the solution of vesicle-forming lipids to an aqueous solution comprising an antigen by injection such that antigen-containing vesicles are formed. 1. A method comprising:providing a molten mixture of vesicle-forming lipids; andadding the molten mixture of vesicle-forming lipids to an aqueous solution comprising an antigen such that antigen-containing vesicles are formed, wherein in the step of adding the molten mixture of vesicle-forming lipids is at a temperature of less than 120° C.2. A method comprising:providing a molten mixture of vesicle-forming lipids; andadding an aqueous solution comprising an antigen to the molten mixture of vesicle-forming lipids such that antigen-containing vesicles are formed, wherein the resulting mixture is placed under temperature-controlled conditions of less than 60° C.3. The method of claim 2 , wherein the molten mixture of vesicle-forming lipids is placed under temperature-controlled conditions of less than 60° C. before step of adding.4. The method of claim 2 , wherein the molten mixture of vesicle-forming lipids is not placed under temperature-controlled conditions of less than 60° ...

METHODS AND SYSTEMS FOR CARDIAC STIMULATION

The present disclosure provides systems and methods for cardiac stimulation. The cardiac stimulation system includes a first cardiac stimulation device implanted in a subject, and a second cardiac stimulation device implanted in the subject and communicatively coupled to the first cardiac stimulation device. The cardiac stimulation system is configured to detect an arrhythmia in the subject, and apply a shocking pulse in response to the detected arrhythmia by supplying a first output voltage from the first cardiac stimulation device and a second output voltage from the second cardiac stimulation device, wherein the first output voltage has a first polarity and the second output voltage has a second polarity that is opposite from the first polarity. 1. A cardiac stimulation system comprising:a first cardiac stimulation device implanted in a subject; and detect an arrhythmia in the subject; and', 'apply a shocking pulse in response to the detected arrhythmia by supplying a first output voltage from the first cardiac stimulation device and a second output voltage from the second cardiac stimulation device, wherein the first output voltage has a first polarity and the second output voltage has a second polarity that is opposite from the first polarity., 'a second cardiac stimulation device implanted in the subject and communicatively coupled to the first cardiac stimulation device, wherein the cardiac stimulation system is configured to2. The system of claim 1 , wherein the first cardiac simulation device comprises a battery configured to provide power to both the first cardiac stimulation device and the second cardiac stimulation device.3. The system of claim 1 , wherein a magnitude of the first output voltage is approximately equal to a magnitude of the second output voltage.4. The system of claim 1 , wherein the first cardiac stimulation device is configured to:switch the polarity of the first output voltage from the first polarity to the second polarity when the ...

Methods for detection of anti-cytomegalovirus neutralizing antibodies

The present disclosure provides methods useful for determining levels of HCMV infection in host cells and, by extension, determining levels of neutralizing antibodies present in a sample. The present disclosure encompasses the recognition that HCMV viruses that have a fluorescent moiety permit detection of viral infection (e.g., by assessing fluorescence in cells after contacting the host cell with the virus). In some embodiments, levels of HCMV infection are determined by fluorescence detection where the virus has been preincubated with a test sample (e.g., a serum sample) from a subject. In some embodiments, the subject has been administered a candidate HCMV vaccine.

SELECTIVE DIFFERENTIATION, IDENTIFICATION, AND MODULATION OF HUMAN TH17 CELLS

The embodiments provide for the modulation of both the differentiation and activity of human Th17 cells. More specifically, human Th17 cell differentiation can modulated by TGF-β and IL-21, and their agonists and antagonists. Function of Th17 cells can be modulated by, for example, BLT1 or podoplanin, and their agonists and antagonists. Additionally, the embodiments provide for the identification of Th17 cells. More specifically, human Th17 cells specifically upregulate BLT1 and podoplanin. 1. A method for modulating the activity of a Th17 cell or Th17 cell population, comprising contacting said cell or population with an amount of Th17 activity modulator sufficient to modulate the activity of a Th17 cell or Th17 cell population, wherein said modulator comprises a podoplanin antagonist or a BLT1 antagonist. This Application is a divisional application of U.S. application Ser. No. 12/863,373 filed on Jul. 16, 2010, which is a 35 U.S.C. §371 National Phase Entry Application of International Application No. PCT/US09/31477 filed Jan. 21, 2009, which designates the U.S., and which claims the benefit of priority from U.S. patent applications Ser. No. 61/006,541, filed Jan. 18, 2008, and Ser. No. 61/031,824, filed Feb. 27, 2008.The invention was made, in part, with government support under grants No. P01 NS038037, No. NS045937 and No. 30843, awarded by the National Institutes of Health. The U.S. government has certain rights in the invention.Autoimmune diseases, more than eighty of which have been identified, cause significant morbidity and disability and are notoriously difficult to diagnose. As many as twenty-four million Americans suffer from autoimmune disease, and treatment costs exceed $100 billion annually.Recently, a new population of effector cells, Th17 cells, has been identified and implicated in various immune-related conditions. The discovery of these cells has had a major impact on the understanding of immune processes not readily explained by the Th1/Th2 ...

METHODS AND COMPOSITIONS FOR THERAPEUTIC AGENTS

The present disclosure provides inter alia compositions that comprise therapeutic agents (e.g., live attenuated viral antigens, therapeutic proteins, etc.) and a lipid component. The lipid component may comprise or consist of different types of lipid or lipids as described herein. In some embodiments the therapeutic agents are thermolabile. The present disclosure also provides methods for preparing compositions, including the aforementioned compositions (e.g., melt methods and spray injection methods among others). 1. A thermostable lyophilized composition comprising:a therapeutic agent; anda lipid component consisting of one or more non-ionic surfactants.2. The composition of claim 1 , wherein the lipid component consists of 1-monopalmitoyl glycerol (MPG).3. A thermostable lyophilized composition comprising:a therapeutic agent; anda lipid component consisting of one or more non-ionic surfactants and one or more steroids.4. The composition of claim 3 , wherein the lipid component consists of 1-monopalmitoyl glycerol (MPG) and cholesterol (CHO).5. A thermostable lyophilized composition comprising:a therapeutic agent; andpre-formed vesicles that comprise a non-ionic surfactant, a steroid and an ionic amphiphile.6. The composition of claim 5 , wherein the ionic amphiphile is dicetylphospate (DCP).7. The composition of claim 5 , wherein the ionic amphiphile is diphosphatidyl glycerol (DPPG).8. The composition of or claim 5 , wherein the non-ionic surfactant is 1-monopalmitoyl glycerol (MPG) and the steroid is cholesterol (CHO).9. A thermostable lyophilized composition comprising:a therapeutic agent; andvesicles that comprise a non-ionic surfactant, a steroid and a phosphoglyceride.10. The composition of claim 9 , wherein the phosphoglyceride is diphosphatidyl glycerol (DPPG).11. The composition of claim 10 , wherein the non-ionic surfactant is 1-monopalmitoyl glycerol (MPG) and the steroid is cholesterol (CHO).1211. The composition of any one of - claims 1 , wherein the ...

Selective differentiation, identification, and modulation of human th17 cells

The embodiments provide for the modulation of both the differentiation and activity of human Th17 cells. More specifically, human Th17 cell differentiation can modulated by TGF-β and IL-21, and their agonists and antagonists. Function of Th17 cells can be modulated by, for example, BLT1 or podoplanin, and their agonists and antagonists. Additionally, the embodiments provide for the identification of Th17 cells. More specifically, human Th17 cells specifically upregulate BLT1 and podoplanin.

COMPOSITIONS AND METHODS FOR TREATMENT OF CYTOMEGALOVIRUS

The present disclosure provides compositions and methods useful for treating HCMV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCMV epitopes, such as, for example, from HCMV envelope glycoproteins gB and/or gH and/or tegument protein pp65. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation). 1. A virus-like particle (VLP) comprising:a first polypeptide that is a murine leukemia virus (MLV) gag polypeptide in that its amino acid sequence includes a portion at least 100, 200, 300 or more amino acids in length that shows at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% identity with a self-assembling portion of a reference MLV gag protein having an amino acid sequence of SEQ ID NO:1; anda second polypeptide whose amino acid sequence includes an epitope recognized by one or more antibodies that bind to a human cytomegalovirus (HCMV) protein.2. The VLP of claim 1 , wherein the second polypeptide has an amino acid sequence that includes an epitope recognized by one or more antibodies to an HCMV glycoprotein B (gB) protein.3. The VLP of claim 1 , wherein the second polypeptide has an amino acid sequence that includes an epitope recognized by one or more antibodies to an HCMV glycoprotein H (gH) protein.43. The VLP of any one of - claims 1 , wherein the second polypeptide has an amino acid sequence comprising a transmembrane claims 1 , a cytoplasmic domain claims 1 , or both.5. The VLP of claim 4 , wherein the transmembrane domain is not found in nature in the HCMV protein.6 ...

METHODS AND COMPOSITIONS FOR THERAPEUTIC AGENTS

The present disclosure provides inter alia compositions that comprise therapeutic agents (e.g., live attenuated viral antigens, therapeutic proteins, etc.) and a lipid component. The lipid component may comprise or consist of different types of lipid or lipids as described herein. In some embodiments the therapeutic agents are thermolabile. The present disclosure also provides methods for preparing compositions, including the aforementioned compositions (e.g., melt methods and spray injection methods among others). 1. A thermostable lyophilized composition comprising:a therapeutic agent; anda lipid component consisting of one or more non-ionic surfactants.2. The composition of claim 1 , wherein the lipid component consists of 1-monopalmitoyl glycerol (MPG).3. A thermostable lyophilized composition comprising:a therapeutic agent; anda lipid component consisting of one or more non-ionic surfactants and one or more steroids.4. The composition of claim 3 , wherein the lipid component consists of 1-monopalmitoyl glycerol (MPG) and cholesterol (CHO).5. A thermostable lyophilized composition comprising:a therapeutic agent; andpre-formed vesicles that comprise a non-ionic surfactant, a steroid and an ionic amphiphile.6. The composition of claim 5 , wherein the ionic amphiphile is dicetylphospate (DCP).7. The composition of claim 5 , wherein the ionic amphiphile is diphosphatidyl glycerol (DPPG).8. The composition of or claim 5 , wherein the non-ionic surfactant is 1-monopalmitoyl glycerol (MPG) and the steroid is cholesterol (CHO).9. A thermostable lyophilized composition comprising:a therapeutic agent; andvesicles that comprise a non-ionic surfactant, a steroid and a phosphoglyceride.10. The composition of claim 9 , wherein the phosphoglyceride is diphosphatidyl glycerol (DPPG).11. The composition of claim 10 , wherein the non-ionic surfactant is 1-monopalmitoyl glycerol (MPG) and the steroid is cholesterol (CHO).12. The composition of any one of - claim 10 , wherein the ...

COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTIONS

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an inactivated virus in combination with a non-ionic surfactant vesicle (NISV). In certain embodiments at least a portion of the antigen present in the composition is physically associated with the NISV. In certain embodiments the compositions are lyophilized and subsequently rehydrated after a period of storage. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV. In certain embodiments the lyophilized compositions are stored at temperatures in excess of 8° C. prior to rehydration. In certain embodiments, the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV and that were also stored at temperatures in excess of 8° C. prior to rehydration. In certain embodiments the antigen is taken from a licensed vaccine and the administered dose of antigen is less than the standard human dose for the licensed vaccine. 119-. (canceled)20. A method of treating an individual suffering from , or at risk for , infection from a polio virus , a rabies virus , a hepatitis A virus or a combination thereof , the method comprising: combining the molten lipids with an aqueous solution comprising an inactivated polio virus, an inactivated rabies virus, an inactivated hepatitis A virus, or a combination thereof;', 'homogenizing the resulting product to produce a homogenized mixture, wherein the molten lipids and aqueous solution are combined in relative amounts and volumes that achieve a lipid concentration of at least about 5 mg/ml in the homogenized mixture;, 'a) melting lipids comprising a non-ionic surfactant comprising 1-monopalmitoyl glycerol to produce molten lipids;'}b) lyophilizing the homogenized mixture to produce a ...

COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTIONS

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an inactivated virus in combination with a non-ionic surfactant vesicle (NISV). In certain embodiments at least a portion of the antigen present in the composition is physically associated with the NISV. In certain embodiments the compositions are lyophilized and subsequently rehydrated after a period of storage. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV. In certain embodiments the lyophilized compositions are stored at temperatures in excess of 8° C. prior to rehydration. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV and that were also stored at temperatures in excess of 8° C. prior to rehydration. In certain embodiments the antigen is taken from a licensed vaccine and the administered dose of antigen is less than the standard human dose for the licensed vaccine. 1. A thermostable lyophilized immunogenic composition comprising:an inactivated viral antigen; anda vesicle which comprises a non-ionic surfactant.2. The composition of claim 1 , where the composition comprises an inactivated polio virus claim 1 , an inactivated rabies virus claim 1 , an inactivated hepatitis A virus claim 1 , or a combination thereof.3. The composition of or claim 1 , wherein the non-ionic surfactant is an ester-linked surfactant.4. The composition of claim 3 , wherein the non-ionic surfactant is a glycerol ester.5. The composition of claim 3 , wherein the non-ionic surfactant is 1-monopalmitoyl glycerol.6. The composition of or claim 3 , wherein the non-ionic surfactant is an ether-linked surfactant.7. The composition of claim 6 , wherein the non-ionic surfactant is a glycol or ...

METHODS FOR DETECTION OF ANTI-CYTOMEGALOVIRUS NEUTRALIZING ANTIBODIES

The present disclosure provides methods useful for determining levels of HCMV infection in host cells and, by extension, determining levels of neutralizing antibodies present in a sample. The present disclosure encompasses the recognition that HCMV viruses that have a fluorescent moiety permit detection of viral infection (e.g., by assessing fluorescence in cells after contacting the host cell with the virus). In some embodiments, levels of HCMV infection are determined by fluorescence detection where the virus has been preincubated with a test sample (e.g., a serum sample) from a subject. In some embodiments, the subject has been administered a candidate HCMV vaccine. 130.-. (canceled)31. A method comprising steps of:(i) mixing heat-inactivated serum from a subject that has been immunized with an HCMV candidate vaccine with an HCMV comprising a fluorescent moiety to form a mixture, wherein the HCMV comprising the fluorescent moiety comprises a gH/gL/gO complex;(ii) adding 10% guinea pig complement to the mixture from (i);(iii) contacting a host cell that is susceptible to infection by HCMV, wherein said host cell is a human foreskin fibroblast cell of cell line HFF-1, under conditions that allow infection with the mixture of heat-inactivated serum in the presence of rabbit complement of (ii);(iv) assessing a fluorescence level of the host cell that has been contacted with the mixture by flow cytometry; and(v) determining a level of infection of the host cell based on the assessed fluorescence level.32. The method of claim 31 , wherein the subject that has been immunized is a human.33. The method of claim 31 , wherein the serum comprises anti-HCMV neutralizing antibodies.34. The method of claim 31 , wherein the HCMV candidate vaccine comprises VLPs.35. The method of claim 34 , wherein the VLPs comprise one or more of gB claim 34 , gH claim 34 , and pp65 from HCMV.36. The method of claim 31 , wherein the mixture of (ii) is incubated for at least 15 minutes claim 31 , ...

COMPOSITIONS AND METHODS FOR TREATING INFLUENZA

The present application provides compositions and methods useful for treating influenza. As described herein, the compositions and methods are based on the development of peptides and peptide combinations which exhibit immunogenic properties against influenza. In some embodiments, the peptide combinations induce a protective response against multiple strains of influenza, e.g., seasonal strains of influenza or even the new pandemic influenza A (H1N1) virus of swine origin. 1. An immunogenic composition comprising:a first peptide comprising a region having at least 80% homology with 20-100 contiguous amino acids of SEQ ID NO. 16, wherein the first peptide includes fewer than 100 contiguous amino acids from a type A influenza hemagglutinin protein;a second peptide comprising an amino acid sequence of SEQ ID NO. 17; anda third peptide comprising a region having at least 80% homology with at least 20 contiguous amino acids from positions 2-49 or 68-121 of SEQ ID NO. 18, wherein the third peptide includes fewer than 100 contiguous amino acids from a type B influenza hemagglutinin protein.2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. The composition of claim 1 , wherein the first peptide comprises at least 40 contiguous amino acids of SEQ ID NO. 6.15. (canceled)16. (canceled)17. (canceled)18. (canceled)19. The composition of claim 1 , wherein the first peptide comprises amino acids 1-88 of SEQ ID NO. 6.20. The composition of claim 1 , wherein the first peptide comprises fewer than 100 amino acids.21. (canceled)22. (canceled)23. The composition of claim 1 , wherein the second peptide comprises an amino acid sequence of SEQ ID NO. 11.24. (canceled)25. (canceled)26. The composition of claim 1 , wherein the composition comprises 2different second peptides each comprising a different amino acid sequence of SEQ ID NO. 11 claim 1 , where n=1-4.2726. The ...

COMPOSITIONS AND METHODS FOR DIAGNOSIS AND TREATMENT OF MALIGNANT GLIOMAS

The present application provides compositions and methods useful for the diagnosing and treating malignant gliomas. As described herein, the compositions and methods are based on the development of HLA class II binding peptides and peptide antigens encoded by the MAGE-A3 and IL-13Rα2 tumor associated genes, which stimulate the activity and proliferation of CD4+ T lymphocytes. In embodiments described herein, the compositions may induce a therapeutic response against malignant gliomas. 1. An immunogenic composition comprising:One or more peptides comprising a region having at least 75% sequence identity with 15-49 contiguous amino acids of SEQ ID NO. 1, wherein the one or more peptides comprises 49 or fewer contiguous amino acids from positions 112-160 of MAGE A3 protein.2. The composition of claim 1 , wherein the one or more peptides comprise a region having at least 80% sequence identity with 15-49 contiguous amino acids of SEQ ID NO. 1.3. The composition of claim 1 , wherein the one or more peptides comprise a region having at least 85% homology with 15-49 contiguous amino acids of SEQ ID NO. 1.4. The composition of claim 1 , wherein the one or more peptides comprise a region having at least 90% homology with 15-49 contiguous amino acids of SEQ ID NO. 1.5. The composition of claim 1 , wherein the one or more peptides comprise a region having at least 95% homology with 15-49 contiguous amino acids of SEQ ID NO. 1.6. The composition of claim 1 , wherein the one or more peptides comprise at least 15 contiguous amino acids of SEQ ID NO. 1.7. An immunogenic composition comprising:one or more peptides comprising a region having at least 75% sequence identity with at least 16-25 contiguous amino acids of SEQ ID NO. 2, wherein the one or more peptides comprises 25 or fewer contiguous amino acids from positions 341-365 of IL-13Rα2 protein.8. The composition of claim 7 , wherein the one or more peptides comprise a region having at least 80% sequence identity with 16-25 ...

VACCINE COMPOSITIONS FOR TREATMENT OF ZIKA VIRUS

The present disclosure provides compositions and methods useful for preventing and treating Zika virus infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more Zika epitopes, such as, for example, from Zika envelope glycoprotein E and the Zika structural protein NS1 including variants thereof. 1. A pharmaceutical composition comprising a virus-like particle (VLP) comprising:a first polypeptide that is a fusion protein comprising an N-terminal portion of a gag protein found in murine leukemia virus (MLV) fused upstream of a modified NS1 protein found in zika virus (ZIKV), said fusion protein having at least 95% identity with the amino acid sequence of SEQ ID NO:19;a second polypeptide having an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; anda pharmaceutically acceptable carrier.2. The pharmaceutical composition of claim 1 , further comprising an adjuvant.3. The pharmaceutical composition of claim 2 , wherein the adjuvant is selected from the group consisting of cytokines claim 2 , gel-type adjuvants claim 2 , microbial adjuvants claim 2 , oil-emulsion and emulsifier-based adjuvants claim 2 , particulate adjuvants claim 2 , synthetic adjuvants claim 2 , polymer adjuvants claim 2 , and/or combinations thereof.4. The pharmaceutical composition of claim 3 , wherein the particulate adjuvant is an aluminum salt.5. The pharmaceutical composition of claim 1 , wherein the composition is characterized in that it induces both humoral and cellular immune responses when administered to a subject.6. The pharmaceutical composition of claim 1 , wherein the VLP is produced by co-transfecting a host cell with a first vector comprising a nucleotide sequence of SEQ ID NO: 20 or 25 and a second vector comprising a nucleotide sequence of SEQ ID NO: 11 or 12; ...

Compositions and methods for treatment of cytomegalovirus

The present disclosure provides compositions and methods useful for treating HCMV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCMV epitopes, such as, for example, from HCMV envelope glycoproteins gB and/or gH and/or tegument protein pp65. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation).

Methods for preparing vesicles and formulations produced therefrom

The present disclosure provides methods for preparing vesicles. In some embodiments, the methods involve providing a molten mixture of vesicle forming lipids and then adding the molten mixture to an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. In other embodiments, the methods involve providing a lyophilized lipid product and rehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. The lyophilized lipid product is prepared by melting vesicle-forming lipids to produce a molten lipid mixture and then lyophilizing the molten lipid mixture. The present disclosure also provides antigen-containing vesicle formulations prepared using these methods. The present disclosure also provides kits that include a lyophilized lipid product in a first container and an aqueous solution comprising an antigen in a second container.

Immunogenic composition, use thereof and method of preparing said composition

composição imunogênica, uso da mesma e método para preparar a referida composição a presente revelação fornece composições e métodos úteis para o tratamento de influenza. como aqui descrito, as composições e os métodos fornecidos se baseiam no desenvolvimento de certas composições que incluem um antígeno de hemaglutinina do vírus influenza em com binação com vesículas lipídicas que incluem um tensoativo não iônico (nisvs) e, opcionalmente, um adjuvante. em certas modalidades, as composições fornecidas permanecem potentes até mesmo quando não são armazenadas em um sistema de cadeia do frio padronizado (ou seja, são termoestáveis). immunogenic composition, use thereof and method of preparing said composition the present disclosure provides compositions and methods useful for treating influenza. as described herein, the compositions and methods provided are based on the development of certain compositions that include an influenza virus hemagglutinin antigen in combination with lipid vesicles that include a non-ionic surfactant (nisvs) and, optionally, an adjuvant. in certain embodiments, the provided compositions remain potent even when they are not stored in a standardized cold chain system (ie, are thermostable).

Compositions and methods for treating viral infections.

La presente invención se refiere a composiciones y métodos útiles para tratar infecciones virales. Como se describe en la presente, las composiciones y métodos se basan en el desarrollo de composiciones inmunogénicas que incluyen un virus atenuado o inactivado con una vesícula de un agente tensoactivo no iónico (NISV).

Compositions and methods for treating viral infections

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an inactivated virus in combination with a non-ionic surfactant vesicle (NISV). In certain embodiments at least a portion of the antigen present in the composition is physically associated with the NISV. In certain embodiments the compositions are lyophilized and subsequently rehydrated after a period of storage. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV. In certain embodiments the lyophilized compositions are stored at temperatures in excess of 8°C prior to rehydration. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV and that were also stored at temperatures in excess of 8°C prior to rehydration. In certain embodiments the antigen is taken from a licensed vaccine and the administered dose of antigen is less than the standard human dose for the licensed vaccine.

Methods and compositions for therapeutic agents

Compositions and methods for treating influenza

The present application provides compositions and methods useful for treating influenza. As described herein, the compositions and methods are based on the development of peptides and peptide combinations which exhibit immunogenic properties against influenza. In some embodiments, the peptide combinations induce a protective response against multiple strains of influenza, e.g., seasonal strains of influenza or even the new pandemic influenza A (H1N1) virus of swine origin.

Methods for preparing vesicles and formulations produced therefrom.

La presente invención se refiere a un método para preparar vesículas que contienen un antígeno que comprende un núcleo acuoso encerrado por una o más bicapas lípidas, dicho método comprende: fundir una mezcla de lípidos que forman una vesícula, dicha mezcla comprende monopalmitoil glicerol (MGP), colesterol (CHO) y fosfato de dicetilo (DCP) en una relación de 5:4:1 a una temperatura de menos de 95°C para formar una mezcla fundida; y agregar la mezcla fundida de lípidos que forman una vesícula a una solución acuosa que comprende un antígeno, de manera que se forman vesículas que contienen el antígeno, en donde las vesículas que contienen el antígeno comprende un núcleo acuoso encerrado por una o más bicapas lípidas y en donde el paso de agregar la mezcla fundida de lípidos que forman una vesícula es a una temperatura de menos que 120°C.

Compositions and methods for treating influenza

The present disclosure provides compositions and methods useful for treating influenza. As described herein, provided compositions and methods are based on the development of certain compositions that include an influenza virus hemagglutinin antigen in combination with lipid vesicles that include a non-ionic surfactant (NISVs) and optionally an adjuvant. In certain embodiments, provided compositions remain potent even when they are not stored in a standard cold-chain system (i.e., they are thermostable).

Cleanout fitting

ABSTRACT OF THE DISCLOSURE A cleanout fitting for use in the construction industry in conjunction with a lateral sewer line to bring the sewer line up to floor level at various locations to facilitate cleaning of the same. The fitting includes a pipe section with internal threads, a plug member with external threads adapted for engagement with the internal threads of the pipe section, a cover plate positionable on top of the pipe section and a connection member for connecting the cover plate with the plug member.

Manhole chimney seal

ABSTRACT An internal seal is disclosed between a manhole casting and mating manhole components such as concrete adjusting rings, the concrete manhole cone, or masonry structure o a similar configuration, to prevent water infiltration at this interface. The seal is formed by a continuous elastomeric ring. The ring is held in place by two stainless steel retaining bands. The elastomeric ring is pleated to allow an upward movement or lateral movement of the casting without impairing the sealing ability of the ring. The gasket can be installed either during construction or at any time after construction that there is found to be a problem with infiltration.

Compositions and methods for treatment of cytomegalovirus

The present disclosure provides compositions and methods useful for treating HCMV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCMV epitopes, such as, for example, from HCMV envelope glycoproteins gB and/or gH and/or tegument protein pp65. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation).

Compositions and methods for treating viral infections

Abstract The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an inactivated virus in combination with a non-ionic surfactant vesicle (NISV). In certain embodiments at least a portion of the antigen present in the composition is physically associated with the NISV. In certain embodiments the compositions are lyophilized and subsequently rehydrated after a period of storage. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV. In certain embodiments the lyophilized compositions are stored at temperatures in excess of 8°C prior to rehydration. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV and that were also stored at temperatures in excess of 8°C prior to rehydration. In certain embodiments the antigen is taken from a licensed vaccine and the administered dose of antigen is less than the standard human dose for the licensed vaccine. 9688389_1 (GHMatters) P97615.AU.1

Compositions and methods for treating viral infections

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an inactivated virus in combination with a non-ionic surfactant vesicle (NISV). In certain embodiments at least a portion of the antigen present in the composition is physically associated with the NISV. In certain embodiments the compositions are lyophilized and subsequently rehydrated after a period of storage. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV. In certain embodiments the lyophilized compositions are stored at temperatures in excess of 8°C prior to rehydration. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV and that were also stored at temperatures in excess of 8°C prior to rehydration. In certain embodiments the antigen is taken from a licensed vaccine and the administered dose of antigen is less than the standard human dose for the licensed vaccine.

Dual intake manifold

Manifold construction

Compositions and methods for treating influenza

The present application provides compositions and methods useful for treating influenza. As described herein, the compositions and methods are based on the development of peptides and peptide combinations which exhibit immunogenic properties against influenza. In some embodiments, the peptide combinations induce a protective response against multiple strains of influenza, e.g., seasonal strains of influenza or even the new pandemic influenza A(H1N1) virus of swine origin.

Compositions and methods for treating influenza

The present application provides compositions and methods useful for treating influenza. As described herein, the compositions and methods are based on the development of peptides and peptide combinations which exhibit immunogenic properties against influenza. In some embodiments, the peptide combinations induce a protective response against multiple strains of influenza, e.g., seasonal strains of influenza or even the new pandemic influenza A(H1N1) virus of swine origin.

Compositions and methods for treatment of cytomegalovirus

Compositions and methods for treating influenza

Methods for preparing thermostable compositions comprising a lipid component and thermolabile therapeutic agents

The present disclosure provides inter alia compositions that comprise therapeutic agents (e.g., live attenuated viral antigens, therapeutic proteins, etc.) and a lipid component. The lipid component may comprise or consist of different types of lipid or lipids as described herein. In some embodiments the therapeutic agents are thermolabile. The present disclosure also provides methods for preparing compositions, including the aforementioned compositions (e.g., melt methods and spray injection methods among others).

Supplementary fluid feed device with automatic tandem metering valves

External manhole chimney seal

ABSTRACT A cylindrical elastomeric seal is disclosed for externally sealing a manhole assembly against surface water infiltration between the manhole casting and the Supporting structure and through the supporting structure. The seal has a first sealing section adapted to receive the edge of the flange of a manhole casting, a second sealing section adapted to be received by the external surface of the manhole chimney or cone, and an intermediate section, joining the two sealing sections, that spans the vertical distance between the casting and the chimney or cone. Sealing means hold the two sealing sections in place against the casting and chimney or cone, creating watertight seals. An extension skirt increases the area the seal can cover, allowing the entire supporting structure to be sealed in the case where the chimney height is too great to be spanned by the inter-mediate section of the seal alone. The seal can be used on old or new construction and does not interfere with normal use of the manhole.

Compositions and methods for treating influenza

The present disclosure provides compositions and methods useful for treating influenza. As described herein, provided compositions and methods are based on the development of certain compositions that include an influenza virus hemagglutinin antigen in combination with lipid vesicles that include a non-ionic surfactant (NISVs) and optionally an adjuvant. In certain embodiments, provided compositions remain potent even when they are not stored in a standard cold-chain system (i.e., they are thermostable).

Therapeutic uses of tim-3 modulators

The invention provides novel methods of treating neurological disorders, including neurodegenerative disorders such as MS. The invention also provides novel methods of treating cancers, including glial tumors such as glioblastoma multiforme. The invention further provides vaccines and related uses.

Compositions and methods for treating influenza.

La presente divulgación proporciona composiciones y métodos útiles para tratar la influenza. Como se describe aquí, las composiciones y métodos proporcionados están basados en el desarrollo de ciertas composiciones que incluyen un antígeno de hemaglutinina del virus de la influenza en combinación con vesículas de lípidos que incluyen un surfactante no iónico (NISVs) y opcionalmente un adyuvante. En ciertas modalidades, las composiciones proporcionadas permanecen en potencia aún cuando no se almacenen en un sistema de cadena fría estándar (es decir, que son termoestables).

Methods for detection of anti-cytomegalovirus neutralizing antibodies

The present disclosure provides methods useful for determining levels of HCMV infection in host cells and, by extension, determining levels of neutralizing antibodies present in a sample. The present disclosure encompasses the recognition that HCMV viruses that have a fluorescent moiety permit detection of viral infection (e.g., by assessing fluorescence in cells after contacting the host cell with the virus). In some embodiments, levels of HCMV infection are determined by fluorescence detection where the virus has been preincubated with a test sample (e.g., a serum sample) from a subject. In some embodiments, the subject has been administered a candidate HCMV vaccine.

Frog point

Compositions and methods for treating influenza

The present disclosure provides compositions and methods useful for treating influenza. As described herein, provided compositions and methods are based on the development of certain compositions that include an influenza virus hemagglutinin antigen in combination with lipid vesicles that include a non-ionic surfactant (NISVs) and optionally an adjuvant. In certain embodiments, provided compositions remain potent even when they are not stored in a standard cold-chain system (i.e., they are thermostable).

Therapeutic uses of TIM-3 modulators

Methods for preparing vesicles and formulations produced therefrom

The present disclosure provides methods for preparing vesicles. In some embodiments, the methods involve providing a molten mixture of vesicle forming lipids and then adding the molten mixture to an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. In other embodiments, the methods involve providing a lyophilized lipid product and rehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. The lyophilized lipid product is prepared by melting vesicle-forming lipids to produce a molten lipid mixture and then lyophilizing the molten lipid mixture. The present disclosure also provides antigen-containing vesicle formulations prepared using these methods. The present disclosure also provides kits that include a lyophilized lipid product in a first container and an aqueous solution comprising an antigen in a second container.

Methods for detection of anti-cytomegalovirus neutralizing antibodies

The present disclosure provides methods useful for determining levels of HCMV infection in host cells and, by extension, determining levels of neutralizing antibodies present in a sample. The present disclosure encompasses the recognition that HCMV viruses that have a fluorescent moiety permit detection of viral infection (e.g., by assessing fluorescence in cells after contacting the host cell with the virus). In some embodiments, levels of HCMV infection are determined by fluorescence detection where the virus has been preincubated with a test sample (e.g., a serum sample) from a subject. In some embodiments, the subject has been administered a candidate HCMV vaccine.

Methods and compositions for therapeutic agents

The present disclosure provides inter alia compositions that comprise therapeutic agents (e.g., live attenuated viral antigens, therapeutic proteins, etc.) and a lipid component. The lipid component may comprise or consist of different types of lipid or lipids as described herein. In some embodiments the therapeutic agents are thermolabile. The present disclosure also provides methods for preparing compositions, including the aforementioned compositions (e.g., melt methods and spray injection methods among others).

Compositions and methods for treating viral infections

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an inactivated virus in combination with a non-ionic surfactant vesicle (NISV). In certain embodiments at least a portion of the antigen present in the composition is physically associated with the NISV. In certain embodiments the compositions are lyophilized and subsequently rehydrated after a period of storage. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV. In certain embodiments the lyophilized compositions are stored at temperatures in excess of 8°C prior to rehydration. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV and that were also stored at temperatures in excess of 8°C prior to rehydration. In certain embodiments the antigen is taken from a licensed vaccine and the administered dose of antigen is less than the standard human dose for the licensed vaccine.

Methods for making and using mass tag standards for quantitative proteomics

Disclosed are methods for producing peptide standards for quantitative proteomics. In one disclosed embodiment, chimeric polypeptides that are a combination of mass tags for multiple proteins are expressed in a host cell that is grown on an isotopically-altered medium. The mass tags in the chimeric polypeptide are separated by specific cleavage sites (such as trypsin cleavage sites), and upon treatment with an appropriate protein cleavage agent (such as trypsin) the constituent peptide standards are released. Methods of mass spectrometric analysis that employ the disclosed chimeric polypeptides (or the peptide standards liberated therefrom) also are disclosed.

Compositions and methods for treatment of hepatitis c

The present disclosure provides compositions and methods useful for treating HCV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCV epitopes, such as, for example, from HCV envelope glycoprotein El and/or E2 or variants thereof (e.g., E2G) and/or non-structural proteins NS3 and/or NS4A. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and interior non-structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation).

Dual carburetor

Methods for detection of anti-cytomegalovirus neutralizing antibodies

Compositions and methods for treating viral infections

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an attenuated or inactivated virus in combination with a non-ionic surfactant vesicle (NISV).

METHOD FOR THE PREPARATION OF VESICLES

MÉTODO PARA A PREPARAÇÃO DE VESÍCULAS. A presente divulgação fornece métodos para a preparação de vesículas. Em algumas modalidades, os métodos envolvem o fornecimento de uma mistura fundida de lipídios formadores de vesículas e então pela adição da mistura fundida em uma solução aquosa compreendendo um antígeno de modo que vesículas contendo antígeno sejam formadas. Em outras modalidades, os métodos envolvem o fornecimento de um produto lipídico liofilizado e reidratação do produto lipídico liofilizado com uma solução aquosa compreendendo um antígeno de modo que as vesículas contendo antígeno sejam formadas. O produto lipídico liofilizado é preparado por fusão dos lipídios formadores de vesículas a fim de produzir uma mistura lipídica fundida e então pela liofilização da mistura lipídica fundida. A presente divulgação também fornece formulações de vesícula contendo antígeno preparadas utilizando esses métodos. A presente divulgação proporciona também kits que incluem um produto lipídico liofilizado em um primeiro recipiente e uma solução aquosa compreendendo um antígeno em um segundo recipiente.

Methods for preparing vesicles and formulations produced therefrom

The present disclosure provides methods for preparing vesicles. In general, these methods include steps of providing a lyophilized lipid product and rehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen- containing vesicles are formed. The lyophilized lipid product is prepared by dissolving vesicle-forming lipids in a polar-protic water-miscible organic solvent to produce a lipid solution and then lyophilizing the lipid solution. The present disclosure also provides antigen-containing vesicle formulations prepared using these methods. The present disclosure also provides kits that include a lyophilized lipid product in a first container and an aqueous solution comprising an antigen in a second container.

Methods for preparing vesicles and formulations produced therefrom

The present disclosure provides methods for preparing vesicles. In one aspect, the methods involve providing a molten mixture of vesicle-forming lipids and adding the molten mixture of vesicle-forming lipids to an aqueous solution comprising an antigen such that antigen-containing vesicles are formed, wherein in the step of adding the molten mixture of vesicle forming lipids is at a temperature of less than 120°C. In another aspect, the methods involve providing a molten mixture of vesicle-forming lipids and adding an aqueous solution comprising an antigen to the molten mixture of vesicle-forming lipids such that antigen-containing vesicles are formed, wherein the resulting mixture is placed under temperature-controlled conditions of less than 60°C. In yet another aspect, the methods involve providing a solution of vesicle forming lipids and adding the solution of vesicle-forming lipids to an aqueous solution comprising an antigen by injection such that antigen-containing vesicles are formed.

Compositions and methods for treatment of cytomegalovirus

5 The present disclosure provides compositions and methods useful for treating HCMV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCMV epitopes, such as, for example, from HCMV envelope 10 glycoproteins gB and/or gH and/or tegument protein pp65. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation). 15

Internal-combustion engine

Engine manifold

Connecting rod

Anderson combination bathroom unit

Engine combustion chamber

Rail frog

Supplementary feed device for internal combustion engines

Supplementary feed device for internal combustion engines

Design for a bathtub

Supplementary fuel feed device

Collar mounted dual actuated fuel feed device

Engine cylinder head

Supplemental fuel feed device

Spirit duplicator or similar article

Supplementary fuel injection system

Design for a cabinet sink

Brake

Apparatus for controlling introduction of supplementary antiknock fuel mixtures

Internal combustion engine

Mounting for supplementary feed device for internal combustion engines

Barometric pressure sensitive engine detonation suppressor