Inactivated virus compositions and methods of preparing such compositions

Abstract

The present invention is directed at a composition comprising a live swine flu virus having an infectious component and a plurality of surface antigens in contact with a formaldehyde donor agent having a molecular weight that is less than about 400 g/mol. Preferably, the formaldehyde donor agent is selected from a non-crosslinking chemical fixative that contains urea.

What is claimed is: 
     
         1 . A method comprising the steps of:
 a) providing a live swine flu virus having an infectious component and a plurality of surface antigens;   b) contacting the swine flu virus with a formaldehyde donor agent haying a molecular weight that is greater than about 50 g/mol and less than about 400 g/mol for a period of time sufficient for de-activating the infectious component with the formaldehyde donor agent, and for preserving at least a portion of the surface antigens to form a deactivated virus.   
     
     
         2 . A method of  claim 1  wherein the virus is grown in a tissue or in vitro cell culture. 
     
     
         3 . A method of  claim 1  or  2  wherein the formaldehyde donor agent is selected from a non-crosslinking chemical fixative that contains urea. 
     
     
         4 . A method of  claim 3  wherein the formaldehyde donor agent is selected from diazolidinyl urea (DU), imidazolidinyl urea (IDU), or a mixture thereof. 
     
     
         5 . A method of any one of  claims 1  to  4  wherein the contacting step includes contacting the virus with the formaldehyde donor agent having a concentration of less than-about w/v (grams per 100 ml total volume) or less. 
     
     
         6 . A method of any one of  claims 1  to  5  wherein the contacting step (b) occurs for a period of about 24 to about 72 hours. 
     
     
         7 . A method of any one of  claims 1  to  6  wherein the contacting step (b) occurs at a temperature of about 23° C. to about 37° C. 
     
     
         8 . A method of any one of  claims 1  to  7  wherein the method is free of any step of contacting the virus with binary ethylene-imine, formaldehyde, formalin, phenol, 2-phenoxyethanol, thimerosal, bromo-ethylene-imine, ethyl methane sulfonate, Nitrosoguanidine, fluorouracil, 5-azacytadine, or any combination thereof. 
     
     
         9 . A method of any one of  claims 1  to  8  wherein the method includes a step of freeze-drying and re-hydrating the antigen-treated virus. 
     
     
         10 . A method of preparing a vaccine comprising the method of any one of  claims 1  to  9  which further comprises; c) mixing a non-toxic effective amount for inducing an immune response in a subject to which the vaccine is administered of the deactivated virus with a pharmaceutically acceptable carrier for forming a vaccine composition. 
     
     
         11 . A method of  claim 10  wherein the virus is an avian virus provided in a live titer amount of about 10 6  to about 10 12  EID 50  per milliliter of the resulting vaccine composition. 
     
     
         12 . A method of  claim 10  or  11  wherein the mixing step (c) occurs immediately following the contacting step (b). 
     
     
         13 . A method according to any one of  claims 1  to  9  wherein the contacted composition is transported or stored at ambient temperature. 
     
     
         14 . A composition comprising a deactivated swine flu virus having an infectious component and a plurality of surface antigens in contact with a formaldehyde donor agent having a molecular weight that is less than about 400 g/mol. 
     
     
         15 . A composition of  claim 14  wherein the virus manufactured by growing the virus in a chicken egg. 
     
     
         16 . A composition of  claim 14  or  15  wherein the formaldehyde donor agent is selected from a non-crosslinking chemical fixative that contains urea. 
     
     
         17 . A composition of any one of  claims 14  to  16  wherein the formaldehyde donor agent is selected from diazolidinyl urea (DU), imidazolidinyl urea (IDU), or a mixture thereof. 
     
     
         18 . A composition of any one of  claims 14  to  17  wherein the formaldehyde donor agent is present in a concentration of less than about 1 w/v (grams per 100 ml total volume) or less. 
     
     
         19 . A composition of any one of  claims 14  to  18  wherein the composition can be transported and stored at ambient temperatures. 
     
     
         20 . A method comprising the steps of:
 a) providing a live swine flu virus having an infectious component and a plurality of surface antigens;   b) contacting the swine flu virus with a formaldehyde donor agent having a molecular weight that is greater than about 50 g/mol and less than about 400 g/mol for a period of time sufficient for de-activating the infectious component with the formaldehyde donor agent, and for preserving at least a portion of the surface antigens to form a deactivated virus   c) transporting or storing the contacted composition at ambient temperature.