Functional epitopes of Streptococcus pneumoniae PsaA antigen and uses thereof
Inventors
Ades, Edwin W. • Sampson, Jacquelyn S. • Steiner, Sandra • Carlone, George M. • Caba, Joseph J. • Rajam, Gowrisankar
Assignees
Centers of Disease Control and Prevention CDC • US Department of Health and Human Services
Publication Number
US-7919104-B2
Publication Date
2011-04-05
Expiration Date
2025-07-29
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Abstract
Provided is a P4 peptide, which contains functional epitopes of the PsaA protein of Streptococcus pneumoniae, 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.
Core Innovation
Streptococcus pneumoniae is a significant cause of global morbidity and mortality, causing diseases such as pneumonia, bacteremia, meningitis, and otitis media primarily in children under 5 years old. While polysaccharide vaccines exist, they are cost-prohibitive for many countries and protect only against prevalent serotypes, leaving a need for a vaccine that protects against all known serotypes. Pneumococcal surface adhesin A (PsaA) is a conserved pneumococcal protein and a vaccine candidate that could be affordable globally.
The invention provides a P4 peptide containing functional epitopes of the PsaA protein of S. pneumoniae and related methods and compositions. The P4 peptide, exemplified by specific sequences such as SEQ ID NO: 1 and SEQ ID NO: 2, contains a functional epitope that mediates bacterial adherence to nasopharyngeal epithelial cells. P4 peptide mimetics having conformational structures identical or similar to P4 are also described. Antibodies specific for the P4 epitope that also specifically bind PsaA are disclosed, as well as immunogenic compositions comprising P4 peptides with pharmaceutical carriers. Methods of using these peptides and antibodies include inhibiting binding of PsaA to cells expressing a PsaA receptor, thereby preventing or treating S. pneumoniae infection.
Claims Coverage
The patent contains six claims, including two independent claims defining isolated peptides and four method claims directed to inhibiting binding and immunogenic compositions. Four main inventive features are identified.
Isolated peptide comprising the amino acid sequence of SEQ ID NO: 1
An isolated peptide that includes the amino acid sequence set forth as SEQ ID NO: 1 representing the P4 peptide functional epitope of PsaA.
Isolated peptide comprising the amino acid sequence of SEQ ID NO: 2
An isolated peptide comprising the amino acid sequence of SEQ ID NO: 2 which is a variant of the P4 peptide with specific amino acid substitutions.
Method of inhibiting binding of PsaA to cells using the isolated peptide SEQ ID NO: 1
A method to inhibit the binding of pneumococcal surface adhesin protein A to cells expressing a PsaA receptor by contacting the cells with the isolated peptide of SEQ ID NO: 1.
Method of inhibiting binding of PsaA to cells using the isolated peptide SEQ ID NO: 2
A method to inhibit the binding of pneumococcal surface adhesin protein A to cells expressing a PsaA receptor by contacting the cells with the isolated peptide of SEQ ID NO: 2.
The claims collectively cover isolated peptides representing the P4 epitope of PsaA and methods of using these peptides to inhibit PsaA binding to its cellular receptor, as well as immunogenic compositions comprising these peptides with pharmaceutical carriers.
Stated Advantages
P4 peptide contains the functional epitope mediating bacterial adherence, enabling improved pneumococcal vaccines.
The isolated P4 peptide allows specific measurement and identification of functional antibodies against S. pneumoniae.
P4 peptide and its mimetics enable effective inhibition of PsaA adherence to nasopharyngeal epithelial cells, aiding prevention and treatment of infection.
The assay format using P4 peptides and coated fluorospheres provides high specificity, reproducibility, and faster data collection for functional antibody evaluation.
Documented Applications
Use of P4 peptide and variants for vaccine compositions to prevent or treat S. pneumoniae infection.
Use of P4-specific antibodies for passive immunization against S. pneumoniae.
Diagnostic assays to detect anti-PsaA or anti-P4 antibodies for current or previous S. pneumoniae infection.
Methods of inhibiting binding of PsaA to nasopharyngeal epithelial cells to prevent bacterial adherence and colonization.
Screening methods to identify antibodies that block PsaA binding or molecules mimicking P4 or PsaA receptor.
Methods to enhance internalization of pneumococci via P4 peptide induced phagocytic activation of cells.
Use of P4 peptide or antibodies in pharmaceutical compositions administered via multiple routes including intranasal delivery.
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