High-yield reassortant influenza vaccine production virus has a mutation at an HLA-A 2.1-restricted CD8+ CTL epitope on the NS1 protein
Graduate School of Biomedical Sciences; Center for Infectious Disease and Vaccine Research
Medical Subject Headings
Base Sequence; CD8-Positive T-Lymphocytes; Genes, Viral; HLA-A Antigens; Humans; Influenza Vaccines; Molecular Sequence Data; Mutation; Orthomyxoviridae; Reassortant Viruses; Viral Nonstructural Proteins
Life Sciences | Medicine and Health Sciences
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 strain used as vaccine seed virus possesses the recent virus HA and NA and contains the internal genes from the high-growing prototype parent. We established 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 observed that there was decreased lysis of target cells infected with the A/Texas/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 that the A/Texas vaccine virus strain contained a quasispecies. Approximately 50% of viral RNA of the NS1 gene had a nucleotide substitution that resulted in the N --> K amino acid change at the sixth position of the nonamer peptide. Current influenza vaccines are inactivated and do not contain the NS1 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 allele, and potentially have reduced efficacy.
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Citation: Virology. 1999 Jun 20;259(1):135-40. Link to article on publisher's site
Terajima, Masanori; Jameson, Julie Marie; Norman, Joyce E.; Cruz, John; and Ennis, Francis A., "High-yield reassortant influenza vaccine production virus has a mutation at an HLA-A 2.1-restricted CD8+ CTL epitope on the NS1 protein" (1999). GSBS Student Publications. 1243.