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

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

Other

George M Carlone

Edwin W Ades

Jacquelyn S Sampson

Sandra Steiner

Harold Russell

Bernard W Beall

Jean A Tharpe

Gowrisankar Rajam

Joseph E Martinez

Scott E Johnson

Danny L Jue

Robert C Huebner

Barun K De

Julie M Skinner

Bonnie B Plikaytis

Maria Da Gloria Carvalho

Karen McCaustland

Nikkol Melnick

Eric L Marston

Jackie S Sampson

Jacqueline S Sampson

Nikkoj Melnick

Katherine E Morrison

Jennifer Crook Whitmon

Michael H Hickey

Carol H Aloisio

Joseph J Caba

Jackie Sampson

Patricia F Holder

Methods for enhancing opsonophagocytosis of a pathogen of interest are disclosed. The disclosed methods include administering to a subject an isolated P4 peptide, which includes the amino acid sequence set forth as SEQ ID NO: 1 and optionally an isolated opsonic antibody or a fragment thereof that specifically binds to an antigen present on the surface of the pathogen of interest. In some examples isolated complement protein or a fragment thereof (for example, a C3a, C3b, iC3b, C3d, C4b, or C5a fragment of a complement protein) is also administered. Compositions containing isolated P4 peptide and one or more isolated opsonic antibodies or a fragment thereof that specifically binds to an antigen present on the surface of a pathogen of interest are also disclosed. In some examples, the compositions also include isolated complement protein or fragment thereof, such as one or more of C3a, C3b, iC3b, C3d, C4b, or C5a.

Use of a pneumococcal P4 peptide for enhancing opsonophagocytosis in response to a pathogen

The invention provides a nucleic acid encoding the 37-kDa pneumococcal surface adhesion A protein (PsaA) from. The invention also provides purified polypeptides encoded by the nucleic acid encoding the 37-kDa protein from and the nucleic acids comprising unique fragment of at least 10 nucleotides of the 37-kDa protein. Additionally, multiple antigenic peptides that provide protection againstchallenge are provided. These multiple antigen peptides comprise the peptides that immunospecifically bind to the monoclonal antibodies. Also provided are vaccines comprising such immunogenic peptides, and methods of conferring protective immunity againstinfection by administering therapeutic composition comprising the immunogenic peptides of the invention. Also provided are methods of detecting the presence ofin a sample using antibodies or antigens and methods of preventing and treatinginfection in a subject.

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This invention, in one aspect, relates to synthetic immunoreactive peptides. These peptides are approximately 20-25 amino acids in length which are portions of the N termini of the M proteins of the most prevalent United States (U.S.) Group A(GAS) serotypes. At least some of the synthetic peptides can be recognized by M type-specific antibodies and are capable of eliciting functional opsonic antibodies and/or anti-attachment antibodies without eliciting tissue cross-reactive antibodies. In another aspect, it relates to compositions or vaccines comprising these synthetic serotype-specific peptides, including polypeptides and proteins. The invention may also be isolated antibodies which are raised in response to the peptides, compositions or vaccines. The invention further relates to kits for using the peptides, compositions, or antibodies. In still further aspects, the invention also relates to methods for using the peptides, compositions, vaccines, or antibodies and methods for tailoring vaccines.

Peptide vaccines against group A streptococci

Methods for enhancing opsonophagocytosis of a pathogen of interest are disclosed. The disclosed methods include administering to a subject an isolated P4 peptide, which includes the amino acid sequence set forth as SEQ ID NO: 1 and optionally an isolated opsonic antibody or a fragment thereof that specifically binds to an antigen present on the surface of the pathogen of interest. In some examples isolated complement protein or a fragment thereof (for example, a C3a, C3b, iC3b, C3d, C4b, or C5a fragment of a complement protein) is also administered. Compositions containing isolated P4 peptide and one or more isolated opsonic antibodies or a fragment thereof that specifically binds to an antigen present of the surface of a pathogen of interest are also disclosed. In some examples, the compositions also include isolated complement protein or fragment thereof, such as one or more of C3a, C3b, iC3b, C3d, C4b, or C5a.

The present invention relates to recombinant lipidated PsaA proteins and recombinant constructs from which such lipidated PsaA proteins may be expressed. The invention relates further to lipidated PsaA proteins in which lipidation is effected by the use of a heterologous leader sequence derived from the ospA gene of, which leader sequence is joined in translational reading frame with the psaA structural gene. The invention also provides methods of preparation of lipidated PsaA proteins and use of such proteins in immunological compositions. Also provided are vaccines comprising immunogenic lipidated PsaA proteins and methods of use of such vaccines in the prevention and treatment ofinfection.

Recombinant lipidated PsaA protein, methods of preparation and use

Provided is a P4 peptide, which contains functional epitopes of the PsaA protein of, and related methods and compositions. P4 peptide mimetics having a conformational structure identical or similar to the conformation of P4 (e.g., SEQ ID NO: 1 and SEQ ID NO:2) are provided. An antibody that specifically binds to the epitope defined by the disclosed peptides is provided. A P4-specific antibody is PsaA-specific since P4 defines an epitope specific for PsaA. Immunogenic compositions comprising the peptide of SEQ ID NO: 1 and a pharmaceutical carrier or the peptide of SEQ ID NO:2 and a pharmaceutical carrier are also provided. Methods of using the peptides and antibodies of the invention are provided.

Peptide vaccines against Group A streptococci

Methods and compositions comprising immunoassays for the detection of antigens and antibodies in a sample are described. In particular, the present invention provides assays that are useful for the rapid and simultaneous detection of multiple different antigens and antibodies. In preferred embodiments, the assays include fluorescent labels of multiple wavelengths or intensities, which are used to label the antigens and antibodies directly and to label beads coated with molecules specific for the antigen or antibody. The detection of a fluorescence shift indicates the presence or identity of the antigen or antibody in the sample.

Methods and compositions for the simultaneous detection of multiple analytes

This application discloses a multivalent opsonophagocytosis assay that does not rely on counting of bacterial colonies to determine bacteria viability following opsonophagocytosis. Instead, the method uses a metabolic colorimetric indicator to determine if viable bacteria are present. Also disclosed are arrays that can be used to determine the viability of bacteria following opsonophagocytosis.

Multiple-valent opsonophagocytic assay selection panel arrays and uses therefor

The present invention relates to recombinant lipidated PsaA proteins and recombinant constructs from which such lipidated PsaA proteins may be expressed. The invention relates further to lipidated PsaA proteins in which lipidation is effected by the use of a heterologous leader sequence derived from the ospA gene ofwhich leader sequence is joined in translational reading frame with the psaA structural gene. The invention also provides methods of preparation of lipidated PsaA proteins and use of such proteins in immunological compositions. Also provided are vaccines comprising immunogenic lipidated PsaA proteins and methods of use of such vaccines in the prevention and treatment ofinfection.

The invention provides a nucleic acid encoding the 37-kDa pneumococcal surface adhesion A protein (PsaA) from. Also provided are isolated nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention also provides purified polypeptides encoded by the nucleic acid encoding the 37-kDa protein from and the nucleic acids comprising unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention further provides monoclonal antibodies which selectively bind PsaA. In addition, peptides are provided that immunospecifically bind to the monoclonal antibodies of the invention, and that are immunogenic againstinfection. Additionally, multiple antigenic peptides that provide protection againstchallenge are provided. These multiple antigen peptides comprise the peptides that immunospecifically bind to the monoclonal antibodies. Also provided are vaccines comprising such immunogenic peptides, and methods of conferring protective immunity againstinfection by administering therapeutic composition comprising the immunogenic peptides of the invention. Also provided are methods of detecting the presence ofin a sample using antibodies or antigens and methods of preventing and treatinginfection in a subject. In addition, a method of identifying the sequence of a peptide potentially capable of eliciting protective immunity against a pathogenic microorganism is provided.

Disclosed are compositions and methods for detecting a specific sequence of the psaA gene using real-time PCR for diagnosis of Pneumococcal Disease.

Development of a real-time PCR assay for detection of pneumococcal DNA and diagnosis of pneumococccal disease

Peptides are disclosed that include SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, or a conservative variant or mimic thereof, wherein the conservative variant or mimic specifically binds an antibody that specifically binds SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID or NO:6. These peptides are of use in generating an immune response against, or in preventing infection with against

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Stone Mountain, GA, United States of America

George M Carlone