Cold-adapted-viral-attenuation (CAVA) and novel attenuated poliovirus strains

A recombinant attenuated temperature-sensitive poliovirus type 1strain that can be propagated in cell culture at 30° C. and cannot be propagated to more than a 5% increase in the number of infectious units for the virus in cell culture at 37° C. wherein the genome of the recombinant attenuated poliovirus strain comprises mutations corresponding to the following positions as compared to the genome of the Mahoney strain (SEQ ID NO:

• 6):
• 131 (A to G), 140 (U to C), 161 (A to G), 593 (C to U), and 605 (G to A) in the 5′UTR;
• and 3482 (G to A), 3848 (A to U), 4116 (U to C), 4424 (A to G), 4559 (A to U), 5432 (G to A), 6206 (A to G), 6844 (G to A), and 7098 (U to C) in the non-structural proteins.

The recombinant attenuated temperature-sensitive poliovirus type 2strain that can be propagated in cell culture at 30° C. and cannot be propagated to more than a 5% increase in the number of infectious units for the virus in cell culture at 37° C., wherein the genome of the recombinant attenuated poliovirus strain comprises mutations corresponding to the following positions as compared to the genome of a MEF-1 strain (SEQ ID NO:

• 5):
• 134 (A to G), 143 (U to C), 164 (A to G), 598 (C to U), and 610 (G to A) in the 5′UTR;
• and 3481 (A to A), 3847 (A to U), 4115 (U to C), 4423 (A to G), 4558 (A to U), 5431 (G to A), 6205 (A to G), 6843 (G to A), and 7097 (U to C) in the non-structural proteins.

The recombinant attenuated temperature-sensitive poliovirus type 3strain that can be propagated in cell culture at 30° C. and cannot be propagated to more than a 5% increase in the number of infectious units for the virus in cell culture at 37° C., wherein the genome of the recombinant attenuated poliovirus strain comprises mutations corresponding to the following positions as compared to the genome of a Saukett strain (SEQ ID NO:

• 7):
• 133 (A to G), 142 (U to C), 163 (A to G), 596 (C to U), and 608 (G to A) in the 5′UTR;
• and 3472 (A to A), 3839 (A to U), 4107 (U to C), 4415 (A to G), 4550 (A to U), 5423 (G to A), 6197 (A to G), 6835 (G to A), and 7089 (U to C) in the non-structural proteins.

The recombinant attenuated temperature-sensitive poliovirus type 1strain that can be propagated in cell culture at 30° C. and cannot be propagated to more than a 5% increase in the number of infectious units for the virus in cell culture at 37° C., wherein the genome of the recombinant attenuated poliovirus strain comprises mutations corresponding to the following positions as compared to the genome of a Sabin 1 strain (SEQ ID NO:

• 9):
• 131 (A to G), 140 (U to C), 161 (A to G), 593 (C to U), and 605 (G to A) in the 5′UTR;
• and 3482 (G to A). 3848 (A to U), 4116 (C to C), 4424 (A to G), 4559 (A to U), 5432 (G to A), 6206 (A to G), 6844 (G to A), and 7098 (U to C) in the non-structural proteins.

A recombinant attenuated temperature sensitive poliovirus type 2 strain that can be propagated in cell culture at 30° C. and cannot be propagated to more than a 5% increase in the number of infectious units for the virus in cell culture at 37° C., wherein the genome of the recombinant attenuated poliovirus strain comprises mutations corresponding to the following positions as compared to the genome of a Sabin 2 strain (SEQ ID NO:

• 10):
• 131 (A to G), 140 (U to C), 161 (A to G), 594 (C to U), and 606 (G to A) in the 5′UTR;
• and 3481 (G to A), 3847 (A to U), 4115 (U to C), 4424 (A to G), 4559 (A to U), 5432 (G to A), 6206 (A to G), 6844 (G to A), and 7098(U to C) in the non-structural proteins.

A recombinant attenuated temperature sensitive poliovirus type 3 strain that can be propagated in cell culture at 30° C. and cannot be propagated to more than a 5% increase in the number of infectious units for the virus in cell culture at 37° C., wherein the genome of the recombinant attenuated poliovirus strain comprises mutations corresponding to the following positions as compared to the genome of a Sabin 3 strain (SEQ ID NO:

• 8):
• 133 (A to G), 142 (U to C), 163 (G to G), 596 (C to U), and 608 (G to A) in the 5′UTR;
• and 3473 (A to A), 3839 (A to U), 4107 (U to C), 4415 (A to G), 4550 (A to U), 5423 (G to A), 6197 (A to G), 6835 (G to A), and 7089(U to C) in the non-structural proteins.