Thermal inactivation of rotavirus

Abstract

Methods of thermally inactivating a rotavirus are provided according to the present invention which include exposing the rotavirus to a temperature in the range of about 50° C.-80° C., inclusive, for an incubation time sufficient to render the rotavirus incapable of replication or infection. The thermally inactivated rotavirus is antigenic and retains a substantially intact rotavirus particle structure. Vaccine compositions and methods of vaccinating a subject against rotavirus are provided which include generation and use of thermally inactivated rotavirus.

We claim: 
     
         1 . A vaccine composition, comprising:
 a) an antigenic thermally-inactivated rotavirus that has a substantially intact rotavirus particle structure and is incapable of replication or infection in a subject, wherein the substantially intact rotavirus particle structure is triple-layer rotavirus particles, double-layer rotavirus particles, or a combination of triple-layer rotavirus particles and double-layer rotavirus particles,   b) an adjuvant; and   c) a sterile pharmaceutically acceptable carrier,   wherein the antigenic thermally-inactivated rotavirus and the adjuvant induce the production of neutralizing antibodies for the rotavirus when administered to a subject.   
     
     
         2 . The vaccine composition of  claim 1 , wherein the adjuvant comprises an AlOH, an AlPO 4 , an aluminum oxide or an aluminum salt. 
     
     
         3 . The vaccine composition of  claim 2 , wherein the adjuvant is AlOH. 
     
     
         4 . The vaccine composition of  claim 2 , wherein the adjuvant is AlPO 4 . 
     
     
         5 . The vaccine composition of  claim 1 , wherein the adjuvant is Freund's adjuvant, iron oxide, saponin, DEAE-dextran, mineral oil, or a bacterial lipopolysaccharide. 
     
     
         6 . The vaccine composition of  claim 1 , wherein the rotavirus is a group A, group B or group C rotavirus. 
     
     
         7 . The vaccine composition of  claim 1 , wherein the rotavirus is an animal rotavirus. 
     
     
         8 . The vaccine composition of  claim 1 , wherein the rotavirus is a human rotavirus. 
     
     
         9 . The vaccine composition of  claim 1 , wherein the rotavirus is a P[8], G1 rotavirus. 
     
     
         10 . The vaccine composition of  claim 1 , further comprising an enteric coating. 
     
     
         11 . The vaccine composition of  claim 10 , wherein the enteric coating comprises a plasticizer. 
     
     
         12 . A method of inducing an immune response to rotavirus in a mammalian subject, comprising:
 administering to the mammalian subject a therapeutically effective amount of the vaccine composition of  claim 1 ,   thereby inducing the immune response to the rotavirus in the mammalian subject.   
     
     
         13 . The method of inducing an immune response to rotavirus of  claim 12 , wherein the mammalian subject is human. 
     
     
         14 . The method of inducing an immune response to rotavirus of  claim 12 , wherein the vaccine composition is administered to the subject by a parenteral route. 
     
     
         15 . The method of inducing an immune response to of  claim 12 , wherein administering the vaccine composition comprises administering at least two doses of the vaccine composition. 
     
     
         16 . The method of  claim 12 , wherein the subject has a rotavirus infection. 
     
     
         17 . The method of  claim 16 , wherein the method reduces the amount of virus shed in feces, reduces the number of days in which the virus is shed in feces, or reduces a symptom of the rotavirus infection. 
     
     
         18 . The method of  claim 12 , wherein the rotavirus is a group A, group B or group C rotavirus. 
     
     
         19 . The method of  claim 12 , wherein the rotavirus is a P[8], G1 rotavirus.