US Government As Represented by the Secretary of the Army

The Liposome Company, Inc.

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.

Entremed, Inc.

The United States of America As Represented by the United States

National Institutes of Health, a Component of the US Dept. of Health & Human Services

The Catholic University of America

Jenner Technologies

Advanced Bioscience Laboratories, Inc.

Jenner Biotherapies, Inc.

The United States of America As Represented by the U.S. Army Medical

Carl R Alving

Gregory M Glenn

Gary R Matyas

Nabila M Wassef

Andrew S Janoff

Alan L Weiner

Mircea C Popescu

Mangala Rao

Glenn M Swartz, Jr

Edgar A Steck

Paul A Tremblay

Robert P Lenk

Michael W Fountain

John W Madsen

Marc J Ostro

Leonard Estis

Lynn D Keyes

Zoltan Beck

Julie Kenner

Marie S Recine

Jean M Muderhwa

Roberta R Owens

Kenner C Rice

Venigalla Basaveswara Rao

Arthur E Jacobson

Malliga R Iyer

Sheetij Dutta

Lynn E Spitler

Thomas C VanCott

Marti Jett-Tilton

Fuying Li

Vaniambadi Kalyanaraman

Alexander V Mayorov

Stephen Whitney

Kejun Cheng

Victoria Polonis

Janos Szebeni

Earl C Richardson

Mary Marovich

Francine McCutchan

Sodsai Tovanabutra

Eric Sanders-Buell

The invention relates to pharmaceutical compositions comprising at least one antigen and an adjuvant composition, where the adjuvant composition comprises a saponin and a liposome. The liposome of the composition comprises monophosphoryl lipid A (MPLA), cholesterol and a phospholipid that is in a liquid crystalline state at greater than or equal to 23&#xb0; C., and the concentration of cholesterol to lipid in the liposome is greater than 50% (mol/mol). The antigen in the composition is a solublerecombinant circumsporozoite protein (rCSP) comprising the amino acid sequence of SEQ ID NO:1, or arCSP peptide that is at least 95% identical to the amino acid sequence of SEQ ID NO:1.

recombinanr xiexumapoeozoite protein compositions and method for vaccine delivery

Provided herein is an adjuvant formulation comprising a monophosphoryl lipid A (MPLA)-containing liposome composition to saponin (e.g., QS-21), wherein the liposome composition comprises i) a lipid bilayer comprising phospholipids in which the hydrocarbon chains have a melting temperature in water of &#x2265;23&#xb0; C. and ii) cholesterol at a mole percent concentration of greater than about 50% (mol/mol), preferably about 55% to about 71% (mol/mol), or more preferably about 55% (mol/mol). The adjuvant formulation displays minimal toxicity of either lipid A or saponin.

Non-toxic adjuvant formulation comprising a monophosphoryl lipid A (MPLA)-containing liposome composition and a saponin

The instant application provides methods and related compositions pertaining to novel HIV envelope proteins. In some embodiments, the invention relates to methods and compositions for the preparation, production, and administration of isolated novel HIV envelope nucleic acid and protein sequences suitable, for example, as vaccines against HIV.

Truncated HIV envelope proteins (ENV), methods and compositions related thereto

In this application is described a composition and method for inducing in a subject anti-hapten antibodies without inducing antibodies to the carrier protein. Kits for designing and making compositions with desired haptens are also described.

Induction of highly specific antibodies to a hapten but not to a carrier peptide by immunization

Antibodies and method of making antibodies, either monoclonal or polyclonal wherein said antibodies have dual or multi-specific binding capacity to more than one type of antigenic epitope. The antibodies have simultaneous or independent recognition subsites to each of the epitopes. Antigenic epitopes include lipids, peptides, proteins, amino acid sequences, sugars and carbohydrates. Monoclonal antibodies and a method of making monoclonal antibodies of the invention include monoclonal antibodies that are broadly neutralizing to HIV-1 or other envelop viruses wherein the monoclonal antibody has subsites that simultaneously recognize protein and lipid epitopes from the virus.

Antibodies with simultaneous subsite specificities to protein and lipid epitopes

Transcutaneous immunization can deliver antigen to the immune system through the stratum corneum without physical or chemical penetration to the dermis layer of the skin. This delivery system induces an antigen-specific immune response without the use of a heterologous adjuvant. This system can induce antigen-specific immune effectors after epicutaneous application of a formulation containing one or more antigensImmune responses that provide prophylactic and/or therapeutic treatments are preferred. Antigenic activities in the formulation may be found in the same molecule, two or more different molecules dissociated from each other, or multiple molecules in a complex formed by covalent or non-covalent bonds. For antigens which are proteinaceous, they may be provided in the formulation as a polynucleotide for transcutaneous genetic immunization. Besides simple application of a dry or liquid formulation to the skin, patches and other medical devices may be used to deliver antigen for immunization.

Transcutaneous immunization without heterologous adjuvant

T4 bacteriophages are bound to substrates such as liposomes using a binder.

T4 bacteriophage bound to a substrate

The invention is a method and assay for detecting human squalene antibodies in sera or plasma using a blocking agent of &#x2212;0.5% casein in a phosphate buffered saline (PBS) solution.

Detection of human antibodies to squalene in serum

A method is provided for inhibiting or preventing toxicity and other unwanted effects (a) caused by solvents for pharmaceuticals which solvents or emulsifier which contain amphiphilic molecules such as polyethoxylated oils or a derivative thereof, or (b) caused by a drug in a vehicle containing amphiphilic molecules such as phopholipids or derivative thereof, emptying a complement inhibitor. Drug compositions containing amphiphilic molecules, or derivatives thereof and a complement inhibitor, and pharmaceutical compositions including a drug, solvent or carrier containing amphiphilic molecules or derivatives thereof, and a complement inhibitor are also provided.

Method of inhibiting side effects of pharmaceutical compositions containing amphiphilic vehicles or drug carrier molecules

A transcutaneous immunization system where the topical application of an adjuvant and an antigen or nucleic acid encoding for an antigen, to intact skin induces a systemic or mucosol antibody response. The immune response so elicited can be enhanced by physical or chemical skin penetration enhancement.

Use of penetration enhancers and barrier disruption methods to enhance the immune response of antigen and adjuvant

The invention is a method for detecting squalene in sera.

Detection of antibodies to squalene in serum

A transcutaneous immunization system delivers antigen to immune cells without perforation of the skin, and induces an immune response in an animal or human. The system uses an adjuvant, preferably an ADP-ribosylating exotoxin, to induce an antigen-specific immune response (e.g., humoral and/or cellular effectors) after transcutaneous application of a formulation containing antigen and adjuvant to intact skin of the animal or human. The efficiency of immunization may be enhanced by adding hydrating agents (e.g., liposomes), penetration enhancers, or occlusive dressings to the transcutaneous delivery system. This system may allow activation of Langerhans cells in the skin, migration of the Langerhans cells to lymph nodes, and antigen presentation.

Adjuvant for transcutaneous immunization

A transcutaneous immunization system where the topical application of an adjuvant and an antigen or nucleic acid encoding for an antigen, to intact skin induces a ystemic or mucosol antibody response. The immune response so elicited can be enhanced by physical or chemical skin penetration enhancement.

Use of penetration enhancers and barrier disruption agents to enhance the transcutaneous immune response

The present invention relates to immunoreactive vaccine compositions for immunizing humans or animals against sterols, such as cholesterol and its derivatives, and their use in methods for reducing the serum cholesterol levels of the immunized individuals and to retard or reduce the severity of artherosclerosis or artherosclerosis plaques caused by ingestion of dietary cholesterol.

Vaccines against sterols

Growing community of inventors

Bethesda, MD, United States of America

Carl R Alving