Pan South American Arenavirus Live Attenuated Vaccine

Abstract

Disclosed herein are methods of making attenuated Arenaviruses, compositions comprising the attenuated Arenaviruses, and methods of using the attenuated Arenaviruses. As disclosed herein, the attenuated Arenaviruses have a deletion of at least a portion of the intergenic region (IGR) of one or both genome segments.

1 . A method of making an IGR Deletion Arenavirus, which comprises deleting at least a portion of an intergenic region (IGR) of one or both genome segments of an Arenavirus, wherein the IGR Deletion Arenavirus is not Car91. 
     
     
         2 . The method according to  claim 1 , wherein the genome segment is the L-segment. 
     
     
         3 . The method according to  claim 1 , wherein at least about 20% of the nucleotide bases of the IGR are deleted. 
     
     
         4 . The method according to  claim 1 , wherein at least about 15-50 nucleotide bases of the IGR are deleted. 
     
     
         5 . The method according to  claim 1 , wherein the IGR has a hairpin loop and deleting the portion of the IGR alters the structure of the hairpin loop. 
     
     
         6 . The method according to  claim 1 , wherein the Arenavirus is a Lassa virus, a Lujo virus, a Lymphocytic choriomeningitis virus, a Chapare virus, a Guanarito virus, a Junin virus, a Machupo virus, a Sabia virus, a Tacaribe virus, or a Whitewater Arroyo virus. 
     
     
         7 . The method according to  claim 1 , wherein the Arenavirus is a Junin virus, a Machupo virus, a Sabia virus, or a Tacaribe virus. 
     
     
         8 . The method according to  claim 1 , wherein the Arenavirus is a Machupo virus. 
     
     
         9 . The method according to  claim 1 , wherein the Arenavirus is JUNV strain Candid#1, MACV strain Carvallo, or MACV strain Chicava. 
     
     
         10 . The method according to  claim 1 , wherein the IGR Deletion Arenavirus is an attenuated form of the Arenavirus. 
     
     
         11 . (canceled) 
     
     
         12 . A composition comprising one or more IGR Deletion Arenaviruses according to  claim 1 . 
     
     
         13 . The composition according to  claim 12 , and further comprising pharmaceutically acceptable carrier. 
     
     
         14 . The composition according to  claim 12 , and further comprising an adjuvant. 
     
     
         15 . A live attenuated vaccine which comprises one or more IGR Deletion Arenaviruses according to  claim 1 . 
     
     
         16 . A method of immunizing a subject against an Arenavirus, which comprises administering to the subject an immunogenic amount of one or more IGR Deletion Arenaviruses according to  claim 1  or a composition thereof. 
     
     
         17 . A method of treating, inhibiting, or reducing an Arenavirus infection or a disease caused by an Arenavirus in a subject, which comprises administering to the subject an effective amount of one or more IGR Deletion Arenaviruses according to  claim 1  or a composition thereof. 
     
     
         18 . The method according to  claim 16 , wherein the administration is before, during, and/or after exposure to the Arenavirus. 
     
     
         19 . The method according to  claim 16 , wherein the Arenavirus and the IGR Deletion Arenavirus are of different viral species. 
     
     
         20 . The method according to  claim 19 , wherein the Arenavirus is a Guanarito virus or a Junin virus and the IGR Deletion Arenavirus is a Machupo virus. 
     
     
         21 . The method according to  claim 16 , wherein the one or more IGR Deletion Arenaviruses elicits a protective immune response against the Arenavirus when administered to the subject.