Virus vaccines

Abstract

Improved mammalian virus vaccines are combinations that contain an immunogenic amount of inactivated virus, such as influenza virus, Herpes varicella virus, measles virus, Epstein Barr virus, respiratory syncytial virus, parainfluenza 3, Herpes simplex type 1 virus, and Herpes simplex type 2 virus, and an immunogenic amount of a purified recombinant envelope protein from the virus, or a fragment or precursor of the protein. Alternatively, they contain either inactivated virus and/or envelope protein antigens and an adjuvant such as granulocyte-microphage colony stimulating factor. One embodiment of an influenza vaccine is prepared by combining inactivated virus, preferably three strains of the virus, and hemagglutinin, preferably a combination of respective hemagglutinins for each of the three strains present. In another embodiment, an influenza vaccine is prepared by combining inactivated virus, again preferably three strains of the virus, and neuraminidase, preferably a combination of respective neuraminidase for each of the three strains present. In a third embodiment, the vaccine contains inactivated virus and both hemagglutinin and neuraminidase, preferably using three strains of each. Granulocyte-macrophage colony stimulating factor is, optionally, added to these embodiments.

I claim:  
     
         1 . An influenza virus vaccine composition for a human being comprising an immunogenic amount of inactivated influenza virus and an immunogenic amount of a purified recombinant envelope protein from the virus, or a fragment or precursor thereof.  
     
     
         2 . A composition according to  claim 1  wherein the recombinant envelope protein is hemagglutinin.  
     
     
         3 . A composition according to  claim 2  wherein the hemagglutinin is uncleaved HA0.  
     
     
         4 . A composition according to  claim 3  wherein the hemagglutinin is produced with recombinant baculovirus vectors in lepidopteran cell cultures and extracted and purified under non-denaturing conditions to at least 90% purity.  
     
     
         5 . A composition according to  claim 1  wherein the inactivated influenza virus comprises three strains of the virus and the recombinant envelope protein comprises at least one hemagglutinin from one strain.  
     
     
         6 . A composition according to  claim 5  wherein the recombinant envelope protein comprises the corresponding hemagglutinins for each strain.  
     
     
         7 . A composition according to  claim 1  wherein the recombinant envelope protein is neuraminidase.  
     
     
         8 . A composition according to  claim 7  wherein the neuraminidase is tetrameric.  
     
     
         9 . A composition according to  claim 8  wherein the neuraminidase is produced with recombinant baculovirus vectors in lepidopteran cell cultures and extracted and purified under non-denaturing conditions to at least 90 % purity.  
     
     
         10 . A composition according to  claim 7  wherein the inactivated influenza virus comprises three strains of the virus and the recombinant envelope protein comprises at least one neuraminidase from one of the strains.  
     
     
         11 . A composition according to  claim 10  wherein the recombinant envelope protein comprises corresponding neuraminidases for each strain.  
     
     
         12 . A composition according to  claim 1  wherein the recombinant envelope protein comprises both neuraminidase and hemagglutinin.  
     
     
         13 . A composition according to  claim 10  wherein the inactivated virus component comprises three strains of the virus and the envelope protein comprises hemagglutinins for at least one of the strains and neuraminidase for at least one of the three strains.  
     
     
         14 . A composition according to  claim 1  further comprising a colony stimulating factor adjuvant.  
     
     
         15 . A composition according to  claim 14  wherein the adjuvant is granulocyte-microphage colony stimulating factor.  
     
     
         16 . A mammalian vaccine composition comprising a combination of at least two components selected from the group consisting of an immunogenic amount of inactivated virus, an immunogenic amount of a purified recombinant envelope protein from said virus, or a fragment or precursor thereof, and an effective amount of a colony stimulating factor.  
     
     
         17 . A composition according to  claim 16  wherein the colony stimulating factor is granulocyte-macrophage colony stimulating factor.  
     
     
         18 . A composition according to  claim 16  wherein the virus is Herpes varicella, the recombinant protein is Herpes varicella envelope glycoprotein D, and the colony stimulating factor is granulocyte-macrophage colony stimulating factor.  
     
     
         19 . A composition according to  claim 16  wherein the virus is measles virus, the colony stimulating factor is granulocyte-macrophage colony stimulating factor, and the recombinant protein is selected from the group consisting of virus envelope F protein, virus envelope G protein, virus envelope FG polyprotein, and mixtures thereof.  
     
     
         20 . A composition according to  claim 16  comprising three strains of inactivated influenza virus and hemagglutinins for each of the three strains, wherein the hemagglutinins are uncleaved HA0 produced with recombinant baculovirus vectors in lepidopteran cell cultures and extracted and purified under non-denaturing conditions to at least 90% purity.  
     
     
         21 . A composition according to  claim 16  comprising three strains of inactivated influenza virus and neuraminidase for each of the three strains, wherein the neruaminidase are tetrameric and produced with recombinant baculovirus vectors in lepidopteran cell cultures and extracted and purified under non-denaturing conditions to at least 90% purity.  
     
     
         22 . A composition according to  claim 16  wherein in the combinations are selected from the group consisting of: 
 (a) inactivated Epstein Barr virus and recombinant virus gp340 envelope protein;  
 (b) inactivated respiratory syncytial virus and a recombinant protein selected from the group consisting of virus envelope F protein, virus envelope G protein, virus envelope FG polyprotein, and mixtures thereof;  
 (c) inactivated parainfluenza 3 virus and a recombinant protein selected from the group consisting of virus envelope F protein, virus envelope G protein, virus envelope FG polyprotein, and mixtures thereof;  
 (d) inactivated Herpes simplex type 1 virus and recombinant virus envelope glycoprotein D; and  
 (e) inactivated Herpes simplex type 2 virus and recombinant virus envelope glycoprotein D.  
 
     
     
         23 . A composition according to  claim 21  further comprising granulocyte-macrophage colony stimulating factor.  
     
     
         24 . A method for immunizing a human being against a virus infection selected from the group consisting of influenza and chicken pox, comprising inoculating the human being with a vaccine composition comprising a combination of at least two components selected from the group consisting of an immunogenic amount of the respective attenuated virus causing the infection, an effective amount of a colony stimulating growth factor, and an immunogenic amount of a purified recombinant envelope protein from said virus, or fragment or precursor thereof.  
     
     
         25 . A method according to  claim 21  wherein the virus is influenza virus, the colony stimulating factor is granulocyte-macrophage colony stimulating factor, and the recombinant envelope protein is selected from the group consisting of hemagglutinin, neuraminidase, and mixtures thereof.  
     
     
         26 . A method according to  claim 24  wherein the vaccine composition comprises three strains of virus and at least one envelope protein corresponding to each strain.