Porin B (PorB) as a therapeutic target for prevention and treatment of infection by chlamydia

Abstract

The present invention features the use of PorB polypeptide as a therapeutic agent. In specific embodiment the invention features a chlamydial vaccine based on a PorB polypeptide, as well as methods for induction of a protective immune response against infection by Chlamydia and Chlamydiophila. The invention further features methods for identifying agents that offset PorB function (e.g., in transport of α-ketoglutarate and which are effective as anti-chlamydial chemotherapeutic agents.

That which is claimed is:  
     
         1 . A method for inducing immunity against Chlamydia in a mammalian subject, the method comprising: 
 administering to a mammalian subject a PorB vaccine in an amount sufficient to elicit an immune response;    wherein said immune response is sufficient to decrease risk of onset of disease caused by Chlamydia.    
     
     
         2 . The method of    claim 1   , wherein the vaccine comprises a PorB polypeptide of  Chlamydia trachomatis.    
     
     
         3 . The method of    claim 1   , wherein the vaccine comprises a PorB polypeptide of  Chlamydia pneumoniae.    
     
     
         4 . The method of    claim 1   , wherein the vaccine comprises a PorB polypeptide of  Chlamydia psittaci.    
     
     
         5 . The method of    claim 1   , wherein the vaccine comprises nucleic acid encoding a PorB polypeptide for expression in the subject.  
     
     
         6 . The method of    claim 1   , wherein the vaccine comprises a recombinant live vaccine which comprises a PorB polypeptide-encoding polynucleotide.  
     
     
         7 . The method of    claim 6   , wherein the live vaccine is a recombinant virus comprising a PorB polypeptide-encoding polynucleotide for expression in the subject.  
     
     
         8 . The method of    claim 1   , wherein the vaccine comprises a PorB polypeptide and said administering is subcutaneous, intramuscular, intradermal, or intravenous.  
     
     
         9 . The method of    claim 1   , wherein the vaccine comprises a nucleic acid encoding a PorB polypeptide and wherein said administering subcutaneous, transdermal, subdermal, intradermal, topical, or intramuscular.  
     
     
         10 . A vaccine composition comprising: 
 an isolated PorB polypeptide in an amount effective to induce an immune response in a subject; and    a pharmaceutically acceptable carrier.    
     
     
         11 . The vaccine composition of    claim 10   , wherein the PorB polypeptide is a PorB polypeptide of  C. trachomatis.    
     
     
         12 . The vaccine composition of    claim 10   , wherein the PorB polypeptide is a PorB polypeptide of  C. pneumoniae.    
     
     
         13 . The vaccine composition of    claim 10   , wherein the PorB polypeptide is a PorB polypeptide of  C. psittaci.    
     
     
         14 . A vaccine composition comprising: 
 an isolated polynucleotide comprising a sequence encoding a PorB polypeptide, the polynucleotide being present in an amount effective to provide for production of the PorB polypeptide in a host in an amount sufficient to induce an immune response in a subject; and    a pharmaceutically acceptable carrier.    
     
     
         15 . The vaccine composition of    claim 14   , wherein the PorB polypeptide is a PorB polypeptide of  C. trachomatis.    
     
     
         16 . The vaccine composition of    claim 14   , wherein the PorB polypeptide is a PorB polypeptide of  C. pneumoniae.    
     
     
         17 . The vaccine composition of    claim 14   , wherein the PorB polypeptide is a PorB polypeptide of  C. psittaci.    
     
     
         18 . A method of providing a subject with protective immunity to chlamydial infection, the method comprising: 
 administering to a subject an amount of an antibody that specifically binds a PorB polypeptide, the amount being effective to inhibit or mitigate chlamydial infection in the subject.    
     
     
         19 . A method for determining exposure of a subject to a Chlamydia infection, the method comprising: 
 contacting a biological sample from a subject suspected having been exposed to Chlamydia or having a Chlamydia infection with a) an antibody that specifically binds a PorB polypeptide or b) a PorB polypeptide, said contacting being under conditions sufficient to allow for formation of specific antibody-PorB polypeptide binding pairs; and    detecting the antibody-PorB binding pairs;    wherein detection of the antibody-PorB binding pairs indicates the subject has been exposed to infection by Chlamydia.    
     
     
         20 . A method for detecting a Chlamydia infection in a subject, the method comprising: 
 contacting a test sample from a subject suspected of having a chlamydial infection with a probe, the probe being selected from the group consisting of a) a PorB polypeptide that can be bound by a PorB-specific antibody, b) a specific PorB antibody; and c) a PorB polypeptide-encoding polynucleotide; and    detecting binding of the probe to the test sample;    wherein detection of binding of the probe to the test sample is indicative of Chlamydia infection in the subject.    
     
     
         21 . The method of    claim 20   , wherein the probe is an anti-PorB antibody for detection of a PorB polypeptide in the test sample.  
     
     
         22 . The method of    claim 20   , wherein the probe is a PorB polypeptide for detection of an anti-PorB antibody in the test sample.  
     
     
         23 . The method of    claim 20   , wherein the probe is a PorB polynucleotide for detection of a PorB polypeptide-encoding polynucleotide in the test sample.  
     
     
         24 . A method for identifying an agent that inhibits PorB function, the method comprising: 
 contacting a PorB polypeptide with a candidate agent; and    determining the effect of the candidate agent on PorB activity in transport of α-ketoglutarate.    
     
     
         25 . The method of    claim 24   , wherein the PorB polypeptide is present in a membrane.  
     
     
         26 . The method of    claim 24   , wherein the membrane is an artificial membrane.  
     
     
         27 . The method of    claim 26   , wherein the artificial membrane is a membrane of a liposome.  
     
     
         28 . The method of    claim 25   , wherein the membrane is an extracellular membrane of a host cell.  
     
     
         29 . A method for identifying an agent that inhibits PorB function, the method comprising: 
 combining a liposome comprising a PorB polypeptide with a candidate agent and α-ketoglutarate; and    determining the effect of the candidate agent on PorB activity in transport of α-ketoglutarate;    wherein a decrease in transport of α-ketoglutarate indicates that the agent inhibits PorB function.