Alphavirus Replicon Particles Matched to Protein Antigens as Immunological Adjuvants

Abstract

The immune response to an antigen of interest, especially one in purified form, can be significantly enhanced by the simultaneous administration of an alphavirus replicon particle which expresses the same antigen. This allows for the use of significantly smaller quantities of the protein antigen than in conventional immunization strategies, and this new immunization strategy can also eliminate the need for boosting administration of the antigen or it can reduce the number of boosts required for an effective immune response to the antigen.

1 . A method of enhancing the immune response to an immunogenic protein in a subject, said method comprising the steps of administering an immunogenic protein to the subject, and further comprising administering alphavirus replicon particles expressing said immunogenic protein. 
     
     
         2 . The method of  claim 1  wherein said immunogenic protein is an influenza virus protein. 
     
     
         3 . The method of  claim 2 , wherein the influenza protein is a hemagglutinin or a neuraminidase. 
     
     
         4 . The method of  claim 1 , wherein the particles are administered simultaneously with or promptly after the administration of the immunogenic protein. 
     
     
         5 . The method of  claim 1 , wherein the particles and the immunogenic protein are administered simultaneously and at the same location. 
     
     
         6 . The method of  claim 1 , wherein the route of administration is subcutaneous, intradermal, intramuscular, intranasal, intraperitoneal, gastrointestinal, rectal, vaginal or via the respiratory mucosa. 
     
     
         7 . The method of  claim 1 , wherein the dose of alphavirus replicon particles is at least 1×10 4  infectious units per ml, as measured by assay on alphavirus-permissive cell culture. 
     
     
         8 . The method of  claim 1 , wherein the alphavirus is VEE. 
     
     
         9 . A method of sparing the dose of an immunogenic protein required to provide effective immunization of a subject comprising administering alphavirus replicon particles capable of expressing said immunogenic protein. 
     
     
         10 . The method of  claim 9 , wherein the dose of alphavirus replicon particles is at least 1×10 4  infectious units per ml, as measured by assay on alphavirus-permissive cell culture. 
     
     
         11 . The method of  claim 10 , wherein the dose of alphavirus replicon particles is at least 1×10 5  infectious units per ml, as measured by assay on alphavirus-permissive cell cultures. 
     
     
         12 . The method of  claim 11 , wherein the dose of alphavirus replicon particles is at least 1×10 6  infectious units per ml, as measured by assay on alphavirus-permissive cell cultures. 
     
     
         13 . The method of  claim 9 , wherein the dose of immunogenic protein used is at least three-fold less than the dose of said immunogenic protein required to provide effective immunization in the absence of alphavirus replicon particles expressing said immunogenic protein. 
     
     
         14 . The method of  claim 9 , wherein the dose of immunogenic protein used is at least five-fold less than the dose of said immunogenic protein required to provide effective immunization in the absence of alphavirus replicon particles expressing said immunogenic protein. 
     
     
         15 . The method of  claim 1 , wherein the immune response is a humoral (i.e. antibody) response and enhancement is at least five-fold. 
     
     
         16 . A method of sparing the dose of alphavirus replicon particles required to provide effective immunization of a subject against an antigen expressed by the particles comprising co-administering the antigen as a protein preparation. 
     
     
         17 . A vaccine composition comprising (a) purified protein and (b) alphavirus replicon particles capable of expressing said protein. 
     
     
         18 . The vaccine composition of  claim 17 , wherein the alphavirus is Venezuelan Equine Encephalitis (VEE) virus. 
     
     
         19 . The vaccine composition of  claim 17 , wherein the protein is an influenza virus protein. 
     
     
         20 . The vaccine composition of  claim 19 , wherein said influenza virus protein is a hemagglutinin or a neuraminidase.