The United States of America, as Represented by the Secretary, Department of Health and Human Services

Other

National Research Council of Canada

New York University

The United States of America as Represented by the Department of Health

John B Robbins

Rachel Schneerson

Joanna Kubler-Kielb

Shousun Chen Szu

Stephen H Leppla

Joseph Shiloach

Fathy Majadly

Zuzana Kossaczka

Darrell T Liu

Louis H Miller

Christopher P Mocca

Evguenii Vinogradov

Xin-Xing Gu

Jerry Lee Keith

Yvonne Ageyman Konadu, Legal Representative

Zuzana Biesova

Mary Jo Rosovitz

Edward S Robbins, Iii

Gary L House

Ruth S Nussenzweig

David J Lim

John D Carlton

Chao-Ming Tsai

Delia M Ramirez

S Dana Hsu

Yimin Wu

Yogendra Singh

Vince Pozsgay

Kurt Klimpel

Gil Ben-Menachem

Haijing Hu

Lily Levi

J N Sarvamangala Devi

Yvonne Ageyman Konadu

Edward Konadu, Deceased

Edward Konadu

Devi J Sarvamangala

Fathy D Majadly

Louis Miller

The disclosure pertains to conjugates of the capsular polysaccharide ofO139, or a structurally and/or immunologically related oligo- or poly-saccharide, and a carrier. These conjugates are useful as pharmaceutical compositions and/or vaccines to induce serum antibodies which have bactericidal (vibriocidal) activity against, in particularO139, and are useful to prevent, treat and/or reduce the severity of disease caused byinfection, such as cholera. The present disclosure also relates to diagnostic tests forinfection, and/or cholera caused byinfection, using one or more of the oligo- or poly-saccharide-carrier conjugates or antibodies described above.

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Disclosed are immunogenic conjugates and therapeutic compositions that include such immunogenic conjugates. Also disclosed are methods of treating and/or inhibiting aninfection. The disclosed immunogenic conjugates have the general structure:Pr&#x2014;Sr&#x2014;O&#x2014;N&#x2550;C-Kdo-OSwherein Pr is a carrier protein, Sr is an optional spacer moiety, Kdo is an 3-deoxy-D-manno-octulosonic acid or a derivative thereof, and OS is an oligosaccharide or polysaccharide obtained from. In specific examples, the immunogenic conjugates include the core oligosaccharide obtained fromhaving the structure:  In specific examples, the disaccharide repeat unit included in the immunogenic conjugate has the structure:&#x3b1;-L-AltNAcA-3-&#x3b2;-FucNAc4N-4-.

Disclosed are immunogenic conjugates which elicit an immune response toproteins. In particular examples, theproteins include sexual stage surface proteins, circumsporozoite protein (CSP), or immunogenic portions of CSP. Also provided herein are immunogenic compositions including one or more of the disclosed immunogenic conjugates and a pharmaceutically acceptable carrier. Further provided is a method of eliciting an immune response toin a subject, comprising administering to the subject an immunogenic composition disclosed herein.

Multicomponent vaccine for malaria providing long-lasting immune responses against plasmodia

Provided are immunogenic compositions and methods for eliciting an immune response againstand other bacteria that contain 3-methyl-3-hydroxybutyrate- or 3-hydroxybutryate-substituted saccharides. Conjugates of 3-methyl-3-hydroxybutyrate- or 3-hydroxybutryate-substituted saccharides elicit an effective immune response againstspores in mammalian hosts to which the conjugates are administered.

Conjugates of ookinete surface protein Pfs25 are provided that are efficacious as vaccines against, the most severe form of malaria. Conjugates of ookinete surface protein Pvs25 for use as a vaccine againstare also provided. Methods for preparing the conjugates, which comprise the ookinete surface protein bound onto itself or onto another protein by a linking group, are also provided.

Vaccine for shigella

The invention relates to improved methods of producing and recoveringprotective antigen (PA), especially modified PA which is protease resistant, and to methods of using of these PAs or nucleic acids encoding these PAs for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of,bacterial infections and which are useful to prevent and/or treat illnesses caused by, such as inhalation anthrax, cutaneous anthrax and gastrointestinal anthrax.

Disclosed are immunogenic conjugates having the general formula:M2e-Cys-S&#x2014;CH&#x2014;C(O)&#x2014;NH&#x2014;CH&#x2014;CH2-C(O&#x2014;)NH-Lys-Pr,were M2e is the influenza M2 ectodomain (M2e) peptide; Cys is a cysteine amino acid residue present in the M2e peptide; S the sulfur present in the cysteine amino acid residue; CH2-CO&#x2014;NH&#x2014;CH2-CH2-CO the linking group; NH the amine group present in a lysine residue of the carrier; Lys is a lysine amino acid residue and Pr the carrier protein. Also disclosed are isolated immunogens that include an immunogenic fragment of an influenza HA protein including the polybasic cleavage site, wherein the immunogenic fragment of the influenza HA protein has been modified to remove an N-terminal leader amino acid sequence and a C-terminal transmembrane domain. Also disclosed are methods producing an influenza vaccine specific for an identified influenza strain.

Vaccines against influenza virus

Methods for making an immunogenic conjugate that includes a hapten or an antigen covalently linked to a carrier. The methods include reacting a first agent with a dihydrazide resulting in a hydrazine-modified first agent, wherein the first agent is a hapten, an antigen or a carrier; reacting a second agent with a benzaldehyde compound resulting in a benzaldehyde-modified second agent, wherein the second agent is a hapten, an antigen or a carrier, provided that the first agent or the second agent is a carrier; and reacting the hydrazine-modified first agent with the benzaldehyde-modified second agent resulting in an immunogenic conjugate comprising a hapten or an antigen covalently linked to a carrier via a hydrazone linkage.

Methods for preparing immunogenic conjugates

The invention relates to improved methods of producing and recovering sporulation-deficientmutant stains, and for producing and recovering recombinantprotective antigen (PA), especially modified PA which is protease resistant, and to methods of using of these PAs or nucleic acids encoding these PAs for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of,bacterial infections and which are useful to prevent and/or treat illnesses caused by, such as inhalation anthrax, cutaneous anthrax and gastrointestinal anthrax.

This invention relates to conjugates of the Vi polysaccharide ofwith the carrierrecombinant exoprotein A (rEPA), and compositions thereof, and to methods of using of these conjugates and/or compositions thereof for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of,bacterial infections. The conjugates, and compositions thereof, are useful as vaccines to induce serum antibodies againstand are useful to prevent and/or treat illnesses caused by

This invention relates to conjugates of the O-specific polysaccharide ofO157 with a carrier, and compositions thereof, and to methods of using of using of these conjugates and/or compositions thereof for eliciting an immunogenic response in mammals, including responses which provide protection against, or reduce the severity of, bacterial infections. More particularly it relates to the use of polysaccharides containing the tetrasaccharide repeat unit: (&#x2192;3)-&#x3b1;-DGalpNAc-(1&#x2192;2)-&#x3b1;-D-PerpNAc-(1&#x2192;3)-&#x3b1;-L-Fucp-(1&#x2192;4)-&#x3b2;-D-Glcp-(1&#x2192;), and conjugates thereof, to induce serum antibodies having bactericidal (killing) activity against hemolytic-uremic syndrome (HUS) causing, in particularO157. The conjugates, and compositions thereof, are useful as vaccines to induce serum antibodies which have bactericidal or bacteriostatic activity against, in particularO157, and are useful to prevent and/or treat illnesses caused byO157. The invention further relates to the antibodies which immunoreact with the O-specific polysaccharide ofO157 and/or the carrier, that are induced by these conjugates and/or compositions thereof. The invention also relates to methods and kits using one or more of the polysaccharides, conjugates or antibodies described above.

Growing community of inventors

Chevy Chase, MD, United States of America

John B Robbins