Constructs for enhancing immune responses

Abstract

Chimeric protein constructs including a herpesvirus glycoprotein D (gD) and a heterologous polypeptide that interact with herpes virus entry mediator (HVEM) and enhance and enhance an immune response against the heterologous polypeptide and methods for their use are provided.

1 . A nucleic acid molecule which encodes a fusion protein comprising:
 a first polypeptide segment comprising at least amino acids 1-240 of a mature Herpes simplex virus (HSV) glycoprotein D, wherein the first polypeptide segment does not comprise a full length mature glycoprotein D;   a second polypeptide segment comprising at least one antigen, wherein the at least one antigen is not an HSV glycoprotein D antigen, wherein the N terminus of the second polypeptide segment is linked to the C terminus of the first polypeptide segment; and   a third polypeptide segment comprising a C terminal portion of the HSV glycoprotein D, wherein the N terminus of the third polypeptide segment is linked to the C terminus of the second polypeptide segment.   
     
     
         2 . The nucleic acid molecule of  claim 1  wherein the HSV is selected from the group consisting of HSV-1 and HSV-2. 
     
     
         3 . The nucleic acid molecule of  claim 2  wherein the first polypeptide segment comprises:
 amino acids 26-265 of SEQ ID NO:27;   amino acids 26-265 of SEQ ID NO:29:   amino acids 1-244 of the glycoprotein D;   amino acids 1-288 of the glycoprotein D; or   amino acids 1-294 of a mature HSV glycoprotein D with the exception that amino acid 294 is alanine instead of tryptophan.   
     
     
         4 . The nucleic acid molecule of  claim 3  which comprises:
 nucleotides 76-795 of SEQ ID NO:26; or   nucleotides 350-1069 of SEQ ID NO:28;   
     
     
         5 - 11 . (canceled) 
     
     
         12 . The nucleic acid molecule of  claim 1  wherein the at least one antigen is selected from the group consisting of:
 an influenza virus antigen;   a nucleoprotein P influenza virus antigen;   a  Plasmodium  antigen;   a  Plasmodium  antigen selected from the group consisting of thrombospondin-related anonymous protein (TRAP), ring-infected erythrocyte surface antigen (RESA), merozoite surface protein 1 (MSP1), merozoite surface protein 2 (MSP2), merozoite surface protein 3 (MSP3), and glutamate-rich antigen (GLURP);   human papilloma virus (HPV) antigen;   human papilloma virus HPV16 antigen;   HPV E5 protein;   HPV E6 protein;   HPV E7 protein;   a human immunodeficiency virus (HIV) antigen; and   an HIV gag antigen.   
     
     
         13 . (canceled) 
     
     
         14 . The nucleic acid molecule of  claim 1  which:
 encodes the amino acid sequence encoded by SEQ ID NO:35;   which comprises SEQ ID NO:35;   which comprises SEQ ID NO:31;   which comprises SEQ ID NO:24;   which comprises SEQ ID NO:34.   
     
     
         15 - 20 . (canceled) 
     
     
         21 . The nucleic acid molecule of  claim 1  wherein;
 the second polypeptide segment comprises the E5 protein, the E6 protein, and the E7 protein;   wherein the fusion protein comprises SEQ ID NO:23;   wherein the fusion protein comprises SEQ ID NO:22;   wherein the fusion protein comprises SEQ ID NO:33.   
     
     
         23 - 30 . (canceled) 
     
     
         31 . The nucleic acid molecule of  claim 1  which:
 is in a viral vector;   which is naked DNA; or   which is in a bacterial vector.   
     
     
         32 - 33 . (canceled) 
     
     
         34 . A fusion protein encoded by the nucleic acid molecule of  claim 1 . 
     
     
         35 - 57 . (canceled) 
     
     
         58 . A method of inducing an immune response, comprising providing to a subject in need thereof a fusion protein of  claim 34 . 
     
     
         59 . The method of  claim 59  wherein the fusion protein is provided by administering to the subject a nucleic acid molecule which encodes the fusion protein. 
     
     
         60 . The method of  claim 59  wherein a nucleic acid molecule of  claim 1  is administered.