Identification and use of high efficacy vaccine antigens which modulate antigen presenting cells

Abstract

The present invention relates to the identification and use of high efficacy vaccine antigens which modulate antigen presenting cells.

1 . A method of making a component of a pharmaceutical comprising: 
 providing an APC;    providing a ligand which interacts with the APC;    contacting the APC with the ligand;    analyzing the activation state of the APC; and    selecting the ligand as the component of a pharmaceutical wherein the ligand superactivates the APC, as determined by the capacity to activate a killer T cell in the absence of a helper T cell.    
   
   
       2 . The method of  claim 1 , wherein the ligand is an antibody selected from the group consisting of FGK45, HM40-3, 3/23, 5C3, Mab-89, BE-1, EA5, and M3.  
   
   
       3 . The method of  claim 1 , wherein the pharmaceutical is formulated in adjuvant or free.  
   
   
       4 . The method of  claim 1 , wherein the APC is a dendritic cell.  
   
   
       5 . The method of  claim 1 , wherein the ligand is provided in the form of a support-bound agent.  
   
   
       6 . A method of making a component of a pharmaceutical comprising: 
 providing an APC;    providing a ligand which interacts with the APC;    contacting the APC with the ligand;    analyzing the activation state of the APC; and    selecting the ligand as the component of a pharmaceutical wherein the ligand inhibits superacetivating the APC, as determined by the capacity to block activating a killer T cell in the absence of a helper T cell.    
   
   
       7 . The method of  claim 6 , wherein the ligand is an antibody selected from the group consisting of 17A10, 2D10, CTLA-4-Ig, and MR1.  
   
   
       8 . The method of  claim 6 , wherein the pharmaceutical is formulated in adjuvant or free.  
   
   
       9 . The method of  claim 6 , wherein the APC is a dendritic cell.  
   
   
       10 . The method of  claim 6 , wherein the ligand is provided in the form of a support-bound agent.  
   
   
       11 . A method of treating or preventing cancer comprising the step of administering a therapeutically effective amount of the pharmaceutical of  claim 1  to a patient in need thereof.  
   
   
       12 . A method of treating or preventing an infection comprising the step of administering a therapeutically effective amount of the pharmaceutical of  claim 1  to a patient in need thereof.  
   
   
       13 . Use of the pharmaceutical of  claim 1  for the manufacture of a medicament for the treatment or prevention of cancer.  
   
   
       14 . Use of the pharmaceutical of  claim 1  for the manufacture of a medicament for treatment or prevention of infection.  
   
   
       15 . A method of making a cancer vaccine component comprising: 
 (a) providing an antigen presenting cell (APC) having a tumor antigen;    (b) providing a ligand which interacts with the APC;    (c) contacting the APC with the ligand;    (d) analyzing the activation state of the APC; and    (e) selecting the ligand as the cancer vaccine component wherein the ligand superactivates the APC, as determined by the capacity to activate a killer T cell in the absence of a helper T cell.    
   
   
       16 . The method of  claim 15 , wherein the ligand is an antibody selected from the group consisting of FGK45, HM40-3, 3/23, 5C3, Mab-89, BE-1, EA5, and M3.  
   
   
       17 . The method of  claim 15 , wherein the cancer vaccine component is formulated in adjuvant or free.  
   
   
       18 . The method of  claim 15 , wherein the APC is a dendritic cell.  
   
   
       19 . The method of  claim 15 , wherein the ligand is provided in the form of a support-bound agent.  
   
   
       20 . A method of treating or preventing cancer comprising the step of administering a therapeutically effective amount of the cancer vaccine component of  claim 15  to a patient in need thereof.  
   
   
       21 . Use of the cancer vaccine component of  claim 15  for the manufacture of a medicament for the treatment or prevention of cancer.  
   
   
       22 . A method of making an anti-pathogen vaccine component comprising: 
 (a) providing an antigen presenting cell (APC);    (b) providing a ligand which interacts with the APC;    (c) contacting the APC with the ligand;    (d) analyzing the activation state of the APC; and    (e) selecting the ligand as the anti-pathogen vaccine component wherein the ligand superactivates the APC, as determined by the capacity to activate a killer T cell in the absence of a helper T cell.    
   
   
       23 . The method of  claim 22 , wherein the ligand is an antibody selected from the group consisting of FGK45, HM40-3, 3/23, 5C3, Mab-89, BE-1, EA5, and M3.  
   
   
       24 . The method of  claim 22 , wherein the anti-pathogen vaccine component is formulated in adjuvant or free.  
   
   
       25 . The method of  claim 22 , wherein the APC is a dendritic cell.  
   
   
       26 . The method of  claim 22 , wherein the ligand is provided in the form of a support-bound agent.  
   
   
       27 . A method of treating or preventing an infection comprising the step of administering a therapeutically effective amount of the anti-pathogen vaccine component of  claim 22  to a patient in need thereof.  
   
   
       28 . Use of the anti-pathogen vaccine component of  claim 22  for the manufacture of a medicament for treatment or prevention of infection.  
   
   
       29 . A method of making a component for immunosupression comprising: 
 (a) providing an antigen presenting cell (APC);    (b) providing a ligand which interacts with the APC;    (c) contacting the APC with the ligand;    (d) analyzing the activation state of the APC; and    (e) selecting the ligand as the component for immunosupression, wherein the ligand inhibits superactivating the APC, as determined by the capacity to block activating a killer T cell in the absence of a helper T cell.    
   
   
       30 . The method of  claim 22 , wherein the ligand is an antibody selected from the group consisting of 17A10, 2D10, CTLA-4-Ig, and MR1.  
   
   
       31 . The method of  claim 29 , wherein the component is formulated in adjuvant or free.  
   
   
       32 . The method of  claim 29 , wherein the APC is a dendritic cell.  
   
   
       33 . The method of  claim 29 , wherein the ligand is provided in the form of a support-bound agent.  
   
   
       34 . A method of activating a killer T cell comprising: 
 providing an APC;    providing a ligand which interacts with the APC;    contacting the ligand with the APC,    analyzing the activation state of the APC;    selecting a superactivated APC; and    contacting the superactivated APC with a killer T cell in the absence of a helper T cell resulting in activation of the killer T cell.    
   
   
       35 . The method of  claim 34 , wherein the ligand is an antibody selected from the group consisting of FGK45, HM40-3, 3/23, 5C3, Mab-89, BE-1, EA5, and M3.  
   
   
       36 . The method of  claim 34 , wherein the APC is a dendritic cell.  
   
   
       37 . A method of identifying immune responsiveness of a subject comprising: 
 (a) providing an APC from the subject;    (b) providing a ligand which interacts with the APC;    (c) contacting the APC with the ligand;    (d) analyzing the activation state of the APC; and    (e) measuring immune responsiveness, wherein the presence of superactivation indicates a good immune responsiveness and wherein the absence of superactivation indicates a poor immune responsiveness.    
   
   
       38 . The method of  claim 37 , wherein the ligand is an antibody selected from the group consisting of FGK45, HM40-3, 3/23, 5C3, Mab-89, BE-1, EA5, M3, 17A10, 2D10, CTLA-4-Ig, and MR1.  
   
   
       39 . The method of  claim 37 , wherein the APC is a dendritic cell.  
   
   
       40 . A kit to identify immune responsiveness comprising: 
 an APC;    a ligand which interacts with the APC;    a means for contacting the APC with the ligand;    a means for analyzing the activation state of the APC; and    a means for measuring immune responsiveness, wherein the presence of superactivation indicates a good immune responsiveness and wherein the absecnce of superactivation indicates a poor immune responsiveness.    
   
   
       41 . The kit of  claim 40 , wherein the ligand is an antibody selected from the group consisting of FGK45, HM40-3, 3/23, 5C3, Mab-89, BE-1, EA5, M3, 17A10, 2D10, CTLA-4-Ig, and MR1.  
   
   
       42 . The kit of  claim 40 , wherein the APC is a dendritic cell.  
   
   
       43 . A method of treating or preventing cancer in a subject comprising: 
 removing an APC from a subject in need of a superactivated APC;    contacting the APC with a cancer cell antigen so as to form an antigen-APC complex;    contacting the antigen-APC complex with a ligand, wherein the ligand superactivates the antigen-APC complex so as to form a superactivated antigen-APC complex; and    administering to the subject a therapeutically effective amount of the superactivated antigen-APC complex.    
   
   
       44 . The method of  claim 43 , wherein the ligand is an antibody selected from the group consisting of FGK45, HM40-3, 3/23, 5C3, Mab-89, BE-1, EA5, and M3.  
   
   
       45 . A method of treating or preventing infection by a pathogen in a subject comprising: 
 removing an APC from a subject in need of a superactivated APC;    contacting the APC with an antigen from the pathogen so as to form an antigen-APC complex;    contacting the antigen-APC complex with a ligand, wherein the ligand superactivates the antigen-APC complex so as to form a superactivated antigen-APC complex; and    administering to the subject a therapeutically effective amount of the superactivated antigen-APC complex.    
   
   
       46 . The method of  claim 45 , wherein the ligand is an antibody selected from the group consisting of FGK45, HM40-3, 3/23, 5C3, Mab-89, BE-1, EA5, and M3.  
   
   
       47 . An isolated biological complex comprising a superactivated antigen presenting cell (APC) attached to a killer T cell and not attached to a helper T cell.  
   
   
       48 . The isolated biological complex of  claim 47 , wherein the APC is a dendritic cell.