Attenuated listeria spp. and methods for using the same

Abstract

Attenuated Listeria bacteria are provided. The subject bacteria are characterized by having a mutation in a gene chosen from the lplA gene and the hly gene. The subject bacteria find use in a variety of applications, where representative applications of interest include, but are not limited to: (a) use of the subject bacteria as adjuvants; (b) use of the subject bacteria as delivery vectors for introducing macromolecules into a cell; (c) use of the subject bacteria as vaccines for eliciting or boosting a cellular immune response; etc.

1 . An attenuated  Listeria  bacterium having a mutation in a gene chosen from the lplA gene and/or the hly gene, wherein when said mutation is in said hly gene, said mutation is not a deletion mutation that removes said hly gene's entire PEST-like sequence coding domain. 
     
     
         2 . The attenuated  Listeria  bacterium according to  claim 1 , wherein said bacterium comprises a mutation in said hly gene. 
     
     
         3 . The attenuated  Listeria  bacterium according to  claim 2 , wherein said mutated hly gene encodes an LLO product that is more hemolytic than wild-type LLO. 
     
     
         4 - 6 . (canceled) 
     
     
         7 . The attenuated  Listeria  bacterium according to  claim 2 , where said mutated hly gene comprises point mutation in said hly gene's PEST-like sequence coding domain. 
     
     
         8 - 10 . (canceled) 
     
     
         11 . The attenuated  Listeria  bacterium according to  claim 1 , wherein said bacterium comprises a mutation in said lplA gene. 
     
     
         12 - 14 . (canceled) 
     
     
         15 . The attenuated  Listeria  bacterium according to  claim 1 , wherein said bacterium comprises a heterologous nucleic acid. 
     
     
         16 . (canceled) 
     
     
         17 . The attenuated  Listeria  bacterium according to  claim 15 , wherein said heterologous nucleic acid encodes at least one product. 
     
     
         18 . The attenuated  Listeria  bacterium according to  claim 17 , wherein said at least one product is an antigen. 
     
     
         19 . A vaccine comprising attenuated  Listeria  bacteria having a mutation in a gene chosen from the lplA gene and/or the hly gene. 
     
     
         20 . The vaccine according to  claim 19 , wherein said mutation is in said hly gene. 
     
     
         21 . The vaccine according to  claim 20 , wherein said mutated hly gene encodes an LLO product that is more hemolytic than wild-type LLO. 
     
     
         22 - 24 . (canceled) 
     
     
         25 . The vaccine according to  claim 20 , where said mutated hly gene comprises point mutation in said hly gene's PEST-like sequence coding domain. 
     
     
         26 - 28 . (canceled) 
     
     
         29 . The vaccine according to  claim 19 , wherein said mutation is in said lplA gene. 
     
     
         30 - 31 . (canceled) 
     
     
         32 . The vaccine according to  claim 19 , wherein said bacteria are  Listeria monocytogenes.    
     
     
         33 . (canceled) 
     
     
         34 . A method of eliciting or boosting a cellular immune response in a subject to an antigen, said method comprising:
 administering to said subject an effective amount of said antigen in conjunction with attenuated  Listeria  bacteria, wherein said attenuated  Listeria  bacteria has a mutation in a gene chosen from the lplA gene and/or the hly gene.   
     
     
         35 . (canceled)