US2019055545A1PendingUtilityA1

Detection of an antibody against a pathogen

Assignee: BRIGHAM & WOMENS HOSPITAL INCPriority: Jan 28, 2016Filed: Jan 27, 2017Published: Feb 21, 2019
Est. expiryJan 28, 2036(~9.5 yrs left)· nominal 20-yr term from priority
C07K 14/415C12N 15/1037C40B 30/04
36
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Claims

Abstract

Provided herein are methods of detecting an antibody directed against a pathogen and uses thereof.

Claims

exact text as granted — not AI-modified
1 . A method for detecting an antibody against a pathogen in a subject, the method comprising:
 (a) contacting a reaction sample comprising a display library with a biological sample comprising antibodies, wherein the display library comprises a plurality of peptides derived from a plurality of pathogens, and   (b) detecting a peptide bound to at least one antibody, thereby detecting an antibody capable of binding the peptide.   
     
     
         2 . The method of  claim 1 , wherein the plurality of pathogens is a plurality of viruses, bacteria or fungi. 
     
     
         3 . The method of  claim 1 , wherein the display library is a phage display library. 
     
     
         4 . The method of  claim 1 , wherein the antibodies in the reaction sample are immobilized. 
     
     
         5 . The method of  claim 1 , wherein the antibodies are immobilized to a solid support adapted for binding IgM, IgA, or IgG subclasses. 
     
     
         6 . The method of  claim 1 , wherein the antibodies are immobilized by contacting the display library and antibodies from the biological sample with Protein A and/or Protein G. 
     
     
         7 . The method of  claim 1 , wherein the Protein A and/or Protein G are immobilized to a solid support. 
     
     
         8 . The method of  claim 1 , comprising removing unbound antibody and peptides of the display library. 
     
     
         9 . The method of  claim 1 , wherein the plurality of peptides are each less than 100, 200, or 300 amino acids long. 
     
     
         10 . The method of  claim 1 , wherein the plurality of peptides are each less than 75 amino acids long. 
     
     
         11 .- 15 . (canceled) 
     
     
         16 . A method for identifying a pathogen associated with a disease, the method comprising
 (a) obtaining a biological sample from a plurality of subjects having a common disease, wherein the common disease is suspected of having a pathogenic component,   (b) separately contacting each sample of a plurality of reaction samples with each biological sample under conditions that allow formation of at least one antibody-peptide complex, wherein the reaction samples each comprise a display library comprising a plurality of peptides derived from a plurality of pathogens,   (c) isolating the at least one antibody-peptide complex formed in each reaction sample from unbound peptides,   (d) correlating at least one peptide in the at least one antibody-peptide complex in each reaction sample to the pathogen from which it is derived, and   (e) identifying a pathogen that is enriched in the plurality of subjects with disease compared to subjects without the disease.   
     
     
         17 . The method of  claim 16 , wherein the plurality of pathogens is a plurality of viruses, bacteria or fungi. 
     
     
         18 . The method of  claim 16 , wherein the display library is a phage display library. 
     
     
         19 . The method of  claim 16 , wherein the antibodies in the reaction sample are immobilized. 
     
     
         20 . The method of  claim 16 , wherein the antibodies are immobilized to a solid support adapted for binding IgM, IgA, or IgG subclasses. 
     
     
         21 . The method of  claim 16 , wherein the antibodies are immobilized by contacting the display library and antibodies from the biological sample with Protein A and/or Protein G. 
     
     
         22 . The method of  claim 16 , wherein the Protein A and/or Protein G are immobilized to a solid support. 
     
     
         23 . The method of  claim 16 , wherein the plurality of peptides are each less than 100 amino acids long. 
     
     
         24 . The method of  claim 16 , wherein the plurality of peptides are each less than 75 amino acids long. 
     
     
         25 .- 31 . (canceled) 
     
     
         32 . A method for improving vaccine design, the method comprising:
 (a) obtaining a biological sample from a plurality of subjects exposed to a pathogen,   (b) separately contacting each sample of a plurality of reaction samples with each biological sample under conditions that allow formation of at least one antibody-peptide complex, wherein the reaction samples each comprise a display library comprising a plurality of peptides derived from a plurality of pathogens,   (c) isolating the at least one antibody-peptide complex formed in each reaction sample from unbound phage,   (d) correlating at least one peptide in the at least one antibody-peptide complex in each reaction sample to the pathogen from which it is derived, and   (e) identifying an antigenic peptide that is enriched in the plurality of subjects exposed to the pathogen as compared to subjects that have not been exposed to the pathogen for use in designing an improved vaccine.   
     
     
         33 .- 54 . (canceled)

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