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 United States

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

Jacquelyn S Sampson

George M Carlone

Edwin W Ades

Harold Russell

Jean A Tharpe

Bernard W Beall

Sandra Steiner

Gowrisankar Rajam

Danny L Jue

Scott E Johnson

Robert C Huebner

Joseph E Martinez

Barun K De

Julie M Skinner

Steven P O'Connor

Nikkoj Melnick

Joseph J Caba

Maria Da Gloria Carvalho

Karen McCaustland

Nikkol Melnick

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

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

The invention provides a nucleic acid encoding the 37-kDa protein 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 a unique fragment of at least 10 nucleotides of the 37-kDa protein. Also provided are antibodies which selectively binds the polypeptides encoded by the nucleic acid encoding the 37-kDa protein and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. Also provided are vaccines comprising immunogenic polypeptides encoded by the nucleic acid encoding the 37-kDa protein and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. Further provided is a method of detecting the presence ofin a sample comprising the steps of contacting a sample suspected of containingwith nucleic acid primers capable of hybridizing to a nucleic acid comprising a portion of the nucleic acid encoding the 37-kDa protein, amplifying the nucleic acid and detecting the presence of an amplification product, the presence of the amplification product indicating the presence ofin the sample. Further provided are methods of detecting the presence ofin a sample using antibodies or antigens, methods of preventing and treatinginfection in a subject.

Multiple antigenic peptides immunogenic against Streptococcus pneumonia

The invention provides a nucleic acid encoding the 37-kDa protein 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 a unique fragment of at least 10 nucleotides of the 37-kDa protein. Also provided are antibodies which selectively binds the polypeptides encoded by the nucleic acid encoding the 37-kDa protein and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. Also provided are vaccines comprising immunogenic polypeptides encoded by the nucleic acid encoding the 37-kDa protein and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. Further provided is a method of detecting the presence of in a sample comprising the steps of contacting a sample suspected of containing with nucleic acid primers capable of hybridizing to a nucleic acid comprising a portion of the nucleic acid encoding the 37-kDa protein, amplifying the nucleic acid and detecting the presence of an amplification product, the presence of the amplification product indicating the presence of in the sample. Further provided are methods of detecting the presence of in a sample using antibodies or antigens, methods of preventing and treating infection in a subject.

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College Park, GA, United States of America

Jacquelyn S Sampson