Method for rapid generation of an attenuated rna virus

A vaccine comprising cDNA fragments, wherein said cDNA fragments are overlapping cDNA fragments obtained by:

• introducing a promoter of DNA-dependent RNA polymerase in position 5′ and optionally a terminator and a RNA polyadenylation sequence in position 3′ of a re-encoded viral genome;
• amplifying said re-encoded viral genome in at least 2, preferably at least 3, 4, 5 or 6 overlapping cDNA fragments;
• wherein said re-encoded viral genome is obtained by re-encoding the viral genome of an infectious RNA virus by randomly substituting a part of the nucleotide codons of the entire viral genome of said infectious RNA virus by another nucleotide codon encoding for the same amino acid,
• with the proviso that:
• the number and position of rare nucleotide codons present in said viral genome are not modified, said rare nucleotide codons being CGU, CGC, CGA, CGG, UCG, CCG, GCG and ACG;
• and
• the regions of said viral genome which are involved with RNA secondary structure are not modified.