Hepatitus A virus vaccines

A method for engineering a live attenuated hepatitis A virus strain adapted to growth in MRC-5 cells comprising the step of modifying an HAV strain by incorporating into the nucleotide sequence of the HAV strain a nucleotide at a nucleotide position homologous to the nucleotide position in the genomic sequence of HM-175, Pass 35, selected from the group consisting of

• (a) at nucleotide position 591 in the 5′ noncoding region of the virus, a G;
• (b) at nucleotide position 646 in the 5′ noncoding region of the virus, an A;
• (c) at nucleotide position 669 in the 5′ noncoding region of the virus, a U or T;
• (d) at nucleotide position 687 in the 5′ noncoding region of the virus, a G;
• (e) at nucleotide position 2750 in the VP1 region of the virus, a T;
• (f) at nucleotide position 3027 in the VP1 region, an A, resulting in the codon at that position encoding Thr;
• (g) at nucleotide position 3934 in the 2B region of the virus, a G;
• (h) at nucleotide position 4418 in the 2C region of the virus, a U or T, resulting in the codon at that position encoding Phe;
• (i) at nucleotide position 4643 in the 2C region of the virus, a U or T;
• (j) at nucleotide position 5145 in the 3A region of the virus, a G, resulting in the codon at that position encoding Val;
• (k) at nucleotide position 5745 in the 3C region of the virus, a U or T, resulting in the codon at that position encoding Ser;
• (l) at nucleotide position 6908 in the 3D region of the virus, a C;
• (m) at nucleotide position 7255 in the 3D region of the virus, a U or T in the 3D region, resulting in the codon at that position encoding Ile;
• and
• (n) any combination of one or more of the nucleotides (a) through (m).