Yeast-Based Vaccine for Inducing an Immune Response

Abstract

The invention provided herein relates to vaccines that can be tailored to achieve a desired immune response. Some compositions provided herein are used for preferentially eliciting a humoral immune response while other compositions are useful for preferentially eliciting a cell-mediated response. Combinations of vaccine compositions are also useful for eliciting both types of responses and/or for modulating the type of immune response elicited. The invention also provides methods for eliciting an immune response in an individual by administering the compositions disclosed herein. These immune responses are useful for protecting an individual from various types of diseases, infections, and undesirable conditions.

1 . A vaccine comprising:
 a) a first yeast vehicle comprising at least one heterologous intracellular antigen; and;   b) a second yeast vehicle comprising at least one heterologous extracellular antigen.   
     
     
         2 . A vaccine comprising:
 a) a first yeast vehicle comprising at least one heterologous intracellular antigen and at least one heterologous extracellular antigen; and   b) a second yeast vehicle comprising at least one heterologous intracellular antigen or at least one heterologous extracellular antigen.   
     
     
         3 . The vaccine of  claim 1 , wherein the intracellular antigen is an antigen that is expressed internally by a pathogen. 
     
     
         4 . The vaccine of  claim 1 , wherein the extracellular antigen is an antigen that is structurally conserved among pathogens of the same type. 
     
     
         5 . The vaccine of  claim 1 , wherein the extracellular antigen is an antigen that is expressed on the surface of a pathogen. 
     
     
         6 . The vaccine of  claim 1 , wherein the extracellular antigen is an antigen that is structurally variable among pathogens of the same type. 
     
     
         7 . The vaccine of  claim 1 , wherein the antigen is from an infectious pathogen. 
     
     
         8 . A vaccine comprising:
 a) a yeast vehicle comprising at least one heterologous intracellular antigen and at least one heterologous extracellular antigen; and   b) a non-yeast-based composition comprising at least one antigen comprised by the yeast vehicle of (a) or an antigen from the same pathogen or disease, wherein the non-yeast-based composition is selected from the group consisting of a DNA vaccine, a protein subunit vaccine, and a killed or inactivated pathogen.   
     
     
         9 . The vaccine of  claim 8 , wherein the yeast vehicle of (a) is formulated for delivery by a different route of administration than the non-yeast-based composition of (b). 
     
     
         10 . A vaccine comprising:
 a) a first yeast vehicle that expresses an influenza virus fusion protein comprising at least a portion of an influenza protein selected from the group consisting of: an influenza matrix (M1) protein, an influenza ion channel protein (M2) and a nucleocapsid (NP) protein; and   b) at least one additional yeast vehicle that expresses an influenza virus fusion protein comprising at least a portion of an influenza protein selected from the group consisting of: a hemagglutinin (HA) protein and a neuraminidase (NA) protein.   
     
     
         11 . The vaccine of  claim 10 , wherein the influenza virus fusion protein comprises at its N-terminus or C-terminus at least a portion of an Aga2 or at least a portion of a Cwp2 protein sufficient to target the fusion protein to the cell wall of the yeast vehicle. 
     
     
         12 . The vaccine of  claim 10 , wherein the yeast vehicle is selected from the group consisting of a whole yeast, a yeast spheroplast, a yeast cytoplast, a yeast ghost, a yeast cell wall preparation, and a subcellular yeast membrane extract or fraction thereof. 
     
     
         13 . The vaccine of  claim 10 , wherein  Saccharomyces  is  S. cerevisiae.    
     
     
         14 . A vaccine comprising:
 a) a yeast vehicle;   b) a first influenza virus fusion protein that is expressed by the yeast vehicle, the first influenza virus fusion protein comprising at least a portion of at least one influenza protein selected from the group consisting of: an influenza matrix (M1) protein, an influenza ion channel protein (M2) and a nucleocapsid (NP) protein; and   c) a second influenza virus fusion protein that is expressed by the yeast vehicle, the second influenza virus fusion protein comprising at least a portion of at least one influenza protein selected from the group consisting of: a hemagglutinin (HA) protein and a neuraminidase (NA) protein.   
     
     
         15 . A method to protect an animal against influenza infection, comprising administering to an animal that has been infected with influenza or is at risk of being infected with influenza, a vaccine according to  claim 14 , wherein administration of the vaccine to the animal reduces or prevents influenza infection or at least one symptom resulting from influenza infection in the animal. 
     
     
         16 . A method to elicit an antigen-specific immune response against an influenza antigen, comprising administering to an animal a vaccine according to  claim 14 . 
     
     
         17 . A method to elicit an antigen-specific immune response, comprising:
 a) administering a first vaccine to an individual, wherein the vaccine comprises a first yeast vehicle that comprises at least one heterologous intracellular antigen and at least one heterologous extracellular antigen, wherein the antigens are associated with the disease or condition; and   b) administering a second vaccine to the individual together with or subsequent to the administration of (a), wherein the second vaccine comprises one or more of:
 i) a second yeast vehicle comprising at least one heterologous antigen used in step (a) or an antigen from the same pathogen or disease, wherein the antigen is extracellular with respect to the second yeast vehicle, or both intracellular and extracellular; 
 ii) a yeast membrane or cell wall particle containing at least one heterologous antigen used in step (a) or an antigen from the same pathogen or disease; 
 iii) a yeast vehicle in admixture with at least one heterologous antigen used in step (a) or an antigen from the same pathogen or disease; 
 iv) a DNA vaccine encoding at least one heterologous antigen used in step (a) or an antigen from the same pathogen or disease; 
 v) a protein subunit vaccine comprising at least one heterologous antigen used in step (a) or an antigen from the same pathogen or disease or an antigen from the same pathogen or disease; or 
 vi) a killed or inactivated pathogen comprising at least one heterologous antigen used in step (a). 
   
     
     
         18 . A method to elicit an antigen-specific immune response in an individual, comprising administering a yeast vehicle to an individual, wherein, prior to or at the time of administering, the individual comprises one or more antigens against which administration of the yeast vehicle elicits an immune response. 
     
     
         19 . The method of  claim 18 , wherein the individual is infected with a pathogen that expresses the one or more antigens. 
     
     
         20 . The method of  claim 18 , wherein the individual has a mutation in a cellular protein against which administration of the yeast vehicle elicits an immune response. 
     
     
         21 . The method of  claim 18 , wherein the yeast vehicle does not express or provide a heterologous antigen.