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

National Research Council of Canada

New York University

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

Other

Rachel Schneerson

John B Robbins

Joanna Kubler-Kielb

Stephen H Leppla

Joseph Shiloach

Fathy Majadly

Darrell T Liu

Louis H Miller

Evguenii Vinogradov

Christopher P Mocca

Robert H Purcell

Zhaochun Chen

Shousun Chen Szu

Jerry Lee Keith

Mary Jo Rosovitz

Zuzana Biesova

Lily Z Dai

Ruth S Nussenzweig

Zuzana Kossaczka

Vince Pozsgay

Gil Ben-Menachem

S Dana Hsu

Delia M Ramirez

Yimin Wu

Mark A Miller

Yogendra Singh

Kurt Klimpel

Teresa Lagergard

Ariel Ginzberg

Haijing Hu

J N Sarvamangala Devi

Lily Levi

Devi J Sarvamangala

Fathy D Majadly

Louis Miller

The present disclosure relates to monoclonal antibodies that bind poly-&#x3b3;-D-glutamic acid (&#x3b3;DPGA), which is present on the surface of. The disclosure also provides chimeric forms of the monoclonal antibodies, humanized forms of the monoclonal antibodies, and fragments thereof, as well as nucleic acids encoding the antibodies and fragments thereof. Pharmaceutical compositions including such antibodies are also disclosed herein. The disclosure further provides prophylactic, therapeutic, and diagnostic methods of using the disclosed antibodies.

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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.

Methods for preparing an oligosaccharide-protein carrier immunogenic conjugate or a polysaccharide-protein carrier immunogenic conjugate. The methods include obtaining an oligosaccharide or polysaccharide having a KDO moiety located at the terminal reducing end of the oligosaccharide or polysaccharide that includes a carbonyl functional group; and reacting the carbonyl functional group of the KDO moiety with an aminooxylated protein carrier molecule resulting in a conjugate that includes a covalent oxime bond between the oligosaccharide and the protein carrier or the polysaccharide and the protein carrier.

Methods for conjugation of oligosaccharides or polysaccharides to protein carriers through oxime linkages via 3-deoxy-D-manno-octulsonic acid

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.

Growing community of inventors

Bethesda, MD, United States of America

Rachel Schneerson