High-yield reassortant influenza vaccine production virus has a mutation at an HLA-A 2.1-restricted CD8(+) CTL epitope on the NS1 protein

Current influenza virus vaccines are prepared using high-yield reassortant virus strains obtained from a mixed infection of the new virus strain and a prototype high-yielding virus strain. The high-titered reassortant virus s train used as vaccine seed virus possesses the recent virus HA and NA and c ontains the internal genes from the high-growing prototype parent. We estab lished a human CD8(+) cytotoxic T cell (CTL) line, 10-2C2, which recognizes an HLA-A2.1-restricted influenza A virus H1, H2, H3 cross-reactive T cell epitope on amino acids 122-130 of the NS1 protein, and unexpectedly we obse rved that there was decreased lysis of target cells infected with the A/Tex as/36/91 (H1N1) vaccine virus strain compared to the lysis of target cells infected with the prototype A/PR/8/34 (H1N1) virus. RT-PCR results showed t hat the A/Texas vaccine virus strain contained a quasispecies. Approximatel y 50% of viral RNA of the NS1 gene had a nucleotide substitution that resul ted in the N --> K amino acid change at the sixth position of the nonamer p eptide. Current influenza vaccines are inactivated and do not contain the N S1 protein; however, future influenza vaccines may include live attenuated vaccines and with this mutation a live virus would fail to induce a CD8(+) CTL response to this epitope in individuals with HLA-A2.1, a very common al lele, and potentially have reduced efficacy. (C) 1999 Academic Press.