Recombinant RSV Virus Expression Systems And Vaccines

Abstract

The present invention relates to genetically engineered recombinant respiratory syncytial viruses and viral vectors which contain deletions of various viral accessory gene(s) either singly or in combination. In accordance with the present invention, the recombinant respiratory syncytial viral vectors and viruses are engineered to contain complete deletions of the M2-2, NS1, NS2, or SH viral accessory genes or various combinations thereof. In addition, the present invention relates to the attenuation of respiratory syncytial virus by mutagenisis of the M2-1 gene.

1 - 35 . (canceled) 
     
     
         36 . An isolated infectious respiratory syncytial virus (RSV) particle having an attenuated phenotype, wherein the particle comprises an RSV antigenome or genome, and wherein the antigenome or genome comprises:
 a M2-2 gene mutation and a SH gene mutation; or   a M2-2 gene mutation and a NS2 gene mutation; or   a NS2 gene mutation and a SH gene mutation.   
     
     
         37 . The isolated infectious RSV particle of  claim 36  wherein the antigenome or genome comprises a M2-2 gene mutation and a SH gene mutation. 
     
     
         38 . The isolated infectious RSV particle of  claim 36  wherein the antigenome or genome comprises a M2-2 gene mutation and a NS2 gene mutation. 
     
     
         39 . The isolated infectious RSV particle of  claim 36  wherein the antigenome or genome comprises a NS2 gene mutation and a SH gene mutation. 
     
     
         40 . The isolated infectious RSV particle of  claim 39  wherein the antigenome or genome further comprises a mutation in gene NS1. 
     
     
         41 . The isolated infectious RSV of  claim 37  wherein the M2-2 gene mutation is a deletion of the M2-2 gene. 
     
     
         42 . The isolated infectious RSV of  claim 37  wherein the SH gene mutation is a deletion of the SH gene. 
     
     
         43 . The isolated infectious RSV of  claim 38  wherein the M2-2 gene mutation is a deletion of the M2-2 gene. 
     
     
         44 . The isolated infectious RSV of  claim 38  wherein the NS2 gene mutation is a deletion of the NS2 gene. 
     
     
         45 . The isolated infectious RSV of  claim 39  wherein the NS2 gene mutation is a deletion of the NS2 gene. 
     
     
         46 . The isolated infectious RSV of  claim 39  wherein the SH gene mutation is a deletion of the SH gene. 
     
     
         47 . The isolated infectious RSV of  claim 40  wherein the mutation in gene NS1 is a deletion of gene NS1. 
     
     
         48 . The isolated infectious RSV of  claim 36  further comprising an L gene mutation. 
     
     
         49 . The isolated infectious RSV of  claim 36  further comprising a heterologous sequence. 
     
     
         50 . The isolated infectious RSV of  claim 49  wherein the heterologous sequence is inserted in the RSV antigenome or genome. 
     
     
         51 . The isolated infectious RSV of  claim 49  wherein the heterologous sequence is substituted for all or a portion of the RSV antigenome or genome. 
     
     
         52 . The isolated infectious RSV of  claim 49  wherein the heterologous sequence is derived from the genome of another strain of RSV. 
     
     
         53 . The isolated infectious RSV of  claim 49  wherein the heterologous sequence is derived from the genome of a virus other than RSV. 
     
     
         54 . An immunogenic composition comprising the isolated infectious RSV particle of  claim 36 .