Alphavirus Vectors for Respiratory Pathogen Vaccines

Abstract

Described herein are compositions and methods for stimulating an immune response to one or more proteins derived from one or more respiratory pathogens. In particular, the invention relates to alphavirus replicons, alphavirus vector constructs, and alphavirus replicon particles expressing one or more antigens derived from one or more respiratory pathogens, as well as to methods of making and using the immunogenic compositions.

1 . An immunogenic composition comprising
 (a) a first alphavirus replicon particle comprising:
 (i) a first heterologous nucleic acid encoding at least one immunogenic protein derived from a first respiratory pathogen; and 
   (b) a second alphavirus replicon particle comprising:
 (ii) a second heterologous nucleic acid encoding at least one immunogenic protein derived from a second respiratory pathogen, 
   wherein the first and second respiratory pathogens are from different species.   
     
     
         2 . The composition of  claim 1  wherein the first respiratory pathogen is a virus selected from the group consisting of an influenza virus, a parainfluenza virus, a respiratory syncytial virus, a human metapneumovirus, and a SARS virus. 
     
     
         3 . The composition of  claim 1  wherein the first respiratory pathogen is a bacteria selected from the group consisting of  Mycobacterium tuberculosis, Corynebacterium diphtheriae, Bordatella pertussis, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Bacillus anthracis , and  Legionella pneumophila.    
     
     
         4 . The composition of  claim 1  wherein each of the first and the second alphavirus replicon particles is derived from an alphavirus independently selected from the group consisting of a Sindbis (SIN) virus, a Semliki Forest virus, a Venezuelan Equine Encephalitis (VEE) virus, a Ross River virus, and a VEE/SIN chimeric alphavirus. 
     
     
         5 . The composition of  claim 1  wherein the first heterologous nucleic acid encodes an influenza virus neuraminidase protein from an influenza virus subtype selected from the group consisting of N1, N2, N3, N4, N5, N6, N7, N8, and N9. 
     
     
         6 . The composition of  claim 1  wherein the first heterologous nucleic acid encodes a parainfluenza virus protein and the second heterologous nucleic acid encodes an influenza virus protein. 
     
     
         7 . The composition of  claim 1  wherein the first heterologous nucleic acid encodes an parainfluenza virus protein and the second heterologous nucleic acid encodes a respiratory syncytial virus protein. 
     
     
         8 . The composition of  claim 1  wherein the first heterologous nucleic acid encodes a respiratory syncytial virus protein and the second heterologous nucleic acid encodes a human metapneumovirus protein. 
     
     
         9 . The composition of  claim 1  wherein the first heterologous nucleic acid encodes an influenza virus protein selected from the group consisting of a hemagglutinin protein, a neuraminidase protein, a nucleocapsid protein, and a matrix protein. 
     
     
         10 . The composition of  claim 1  wherein the first heterologous nucleic acid encodes a SARS virus protein selected from the group consisting of a spike protein, an envelope protein, a nucleocapsid protein, and a matrix protein. 
     
     
         11 . The composition of  claim 1  wherein the first heterologous nucleic acid encodes a a human metapneumovirus protein selected from the group consisting of a glycoprotein G, a nucleocapsid protein, and a matrix protein. 
     
     
         12 . The composition of  claim 1  wherein the first heterologous nucleic acid encodes a parainfluenza virus protein selected from the group consisting of a hemagglutinin-neuraminidase protein, a nucleocapsid protein, and a matrix protein. 
     
     
         13 . The composition of  claim 1  wherein the first heterologous nucleic acid encodes a respiratory syncytial virus protein selected from the group consisting of a glycoprotein G, a nucleocapsid protein, and a matrix protein. 
     
     
         14 . An immunogenic composition comprising an alphavirus replicon vector comprising:
 (a) a first heterologous nucleic acid encoding at least one immunogenic protein derived from a first respiratory pathogen; and   (b) a second heterologous nucleic acid encoding at least one immunogenic protein derived from a second respiratory pathogen,   
       wherein the first and second respiratory pathogens are from different species. 
     
     
         15 . The composition of  claim 14  wherein the first respiratory pathogen is a parainfluenza virus and the second respiratory pathogen is an influenza virus. 
     
     
         16 . The composition of  claim 14  wherein the first respiratory pathogen is a parainfluenza virus and the second respiratory pathogen is a respiratory syncytial virus. 
     
     
         17 . A method of stimulating an immune response in a mammal, comprising administering to a mammal the immunogenic composition of  claim 1 . 
     
     
         18 . The method of  claim 17  further comprising the step of administering a second immunogenic composition. 
     
     
         19 . A method of stimulating an immune response in a mammal, comprising administering to the mammal the immunogenic composition of  claim 14 . 
     
     
         20 . The method of  claim 19  further comprising the step of administering a second immunogenic composition.