Compounds and methods for treatment and diagnosis of chlamydial infection

Abstract

Compounds and methods for the diagnosis and treatment of Chlamydial infection are disclosed. The compounds provided include polypeptides that contain at least one antigenic portion of a Chlamydia antigen and DNA sequences encoding such polypeptides. Pharmaceutical compositions and vaccines comprising such polypeptides or DNA sequences are also provided, together with antibodies directed against such polypeptides. Diagnostic kits containing such polypeptides or DNA sequences and a suitable detection reagent may be used for the detection of Chlamydial infection in patients and in biological samples.

1 . An isolated polynucleotide comprising a sequence selected from the group consisting of: 
 (a) sequences provided in SEQ ID NO: 158-166;    (b) complements of the sequences provided in SEQ ID NO: 158-166;    (c) sequences consisting of at least 20 contiguous residues of a sequence provided in SEQ ID NO: 158-166;    (d) sequences that hybridize to a sequence provided in SEQ ID NO: 158-166, under highly stringent conditions;    (e) sequences having at least 95% identity to a sequence of SEQ ID NO: 158-166;    (f) sequences having at least 99% identity to a sequence of SEQ ID NO: 158-166; and    (g) degenerate variants of a sequence provided in SEQ ID NO: 158-166.    
     
     
         2 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) sequences encoded by a polynucleotide of  claim 1;     (b) sequences having at least 95% identity to a sequence encoded by a polynucleotide of  claim 1;  and    (c) sequences having at least 99% identity to a sequence encoded by a polynucleotide of  claim 1 .    
     
     
         3 . An isolated polypeptide comprising at least an immunogenic fragment of a polypeptide sequence selected from the group consisting of: 
 (a) a polypeptide sequence set forth in SEQ ID NO: 167-175,    (b) a polypeptide sequence having at least 95% identity with a sequence set forth in SEQ ID NO: 167-175;    (c) a polypeptide sequence having at least 99% identity with a sequence set forth in SEQ ID NO: 167-175; and    (d) sequences consisting of at least 10 contiguous residues of a sequence provided in SEQ ID NO: 167-175.    
     
     
         4 . An expression vector comprising a polynucleotide of  claim 1  operably linked to an expression control sequence.  
     
     
         5 . A host cell transformed or transfected with an expression vector according to  claim 4 .  
     
     
         6 . An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a polypeptide of  claim 2  or  claim 3 .  
     
     
         7 . A method for detecting the presence of  Chlamydia  in a patient, comprising the steps of: 
 (a) obtaining a biological sample from the patient;    (b) contacting the biological sample with a binding agent that binds to a polypeptide of  claim 2  or  claim 3;     (c) detecting in the sample an amount of polypeptide that binds to the binding agent; and    (d) comparing the amount of polypeptide to a predetermined cut-off value and therefrom determining the presence of  Chlamydia  in the patient.    
     
     
         8 . A fusion protein comprising at least one polypeptide according to  claim 2  or  claim 3 .  
     
     
         9 . An oligonucleotide that hybridizes to a sequence recited in any one of SEQ ID NO: 158-166 under highly stringent conditions.  
     
     
         10 . A method for stimulating and/or expanding T cells specific for a  Chlamydia  protein, comprising contacting T cells with at least one component selected from the group consisting of: 
 (a) a polypeptide according to  claim 2  or  claim 3;     (b) a polynucleotide according to  claim 1;  and    (c) an antigen-presenting cell that expresses a polynucleotide according to  claim 1 ,    under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.    
     
     
         11 . An isolated T cell population, comprising T cells prepared according to the method of  claim 10 .  
     
     
         12 . A composition comprising a first component selected from the group consisting of physiologically acceptable carriers and immunostimulants, and a second component selected from the group consisting of: 
 (a) a polypeptide according to  claim 2  or  claim 3;     (b) a polynucleotide according to  claim 1;     (c) an antibody according to  claim 6;     (d) a fusion protein according to  claim 8;     (e) a T cell population according to  claim 11;  and    (f) an antigen presenting cell that expresses a polypeptide according to  claim 2  or  claim 3 .    
     
     
         13 . A method for stimulating an immune response in a patient, comprising administering to the patient a composition selected from the group consisting of: 
 (a) a composition of  claim 12;     (b) a polynucleotide sequence of any one of SEQ ID NO:158-166; and    (c) a polypeptide sequence of any one of SEQ ID NO:167-175.    
     
     
         14 . A method for the treatment of  Chlamydia  infection in a patient, comprising administering to the patient a composition selected from the group consisting of: 
 (a) a composition of  claim 12;     (b) a polynucleotide sequence of any one of SEQ ID NO:158-166; and    (c) a polypeptide sequence of any one of SEQ ID NO:167-175.    
     
     
         15 . A method for determining the presence of  Chlamydia  in a patient, comprising the steps of: 
 (a) obtaining a biological sample from the patient;    (b) contacting the biological sample with an oligonucleotide according to  claim 9;     (c) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; and    (d) comparing the amount of polynucleotide that hybridizes to the oligonucleotide to a predetermined cut-off value, and therefore determining the presence of the cancer in the patient.    
     
     
         16 . A diagnostic kit comprising at least one oligonucleotide according to  claim 9 .  
     
     
         17 . A diagnostic kit comprising at least one antibody according to  claim 6  and a detection reagent, wherein the detection reagent comprises a reporter group.  
     
     
         18 . A method for the treatment of  Chlamydia  in a patient, comprising the steps of: 
 (a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of:    (i) a polypeptide according to any one of claims  2  or  3 ;    (ii) a polypeptide sequence of any one of SEQ ID NO: 167-175;    (iii) a polynucleotide according to  claim 1;     (iv) a polynucleotide sequence of any one of SEQ ID NO:158-166;    (v) an antigen presenting cell that expresses a polypeptide sequence set forth in any one of claims  2  or  3 ;    (vi) an antigen presenting cell that expresses a polypeptide sequence of any one of SEQ ID NO:167-175, such that the T cells proliferate; and    (b) administering to the patient an effective amount of the proliferated T cells.