High-Yield Reassortant Influenza Vaccine Production Virus Has a Mutation at an HLA-A 2.1-Restricted CD8+ CTL Epitope on the NS1 Protein
Identifieur interne : 001A27 ( Main/Exploration ); précédent : 001A26; suivant : 001A28High-Yield Reassortant Influenza Vaccine Production Virus Has a Mutation at an HLA-A 2.1-Restricted CD8+ CTL Epitope on the NS1 Protein
Auteurs : Masanori Terajima ; Julie Jameson ; Joyce E. Norman ; John Cruz ; Francis A. EnnisSource :
- Virology [ 0042-6822 ] ; 1999.
English descriptors
- Teeft :
- Amino, Amino acid change, Amino acid sequence, Amino acid sequences, Amino acid substitution, Amino acids, Assay, Cell assays, Cell clone, Cell epitope, Clinical study, Clone, Cytotoxic, Epitope, Influenza, Influenza vaccines, Influenza virus, Internal genes, Jameson, Kilbourne, Lysis, Mutation, Nonamer, Nonamer peptide, Nucleotide, Nucleotide sequence, Nucleotide sequences, Peptide, Primer, Reassortant, Reassortant virus, Sixth position, Target cells, Vaccine, Vaccine strain, Vaccine virus, Vaccine virus strain, Virus, Virus strain.
Abstract
Abstract: 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.
Url:
DOI: 10.1006/viro.1999.9719
Affiliations:
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Le document en format XML
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<term>Reassortant</term>
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<front><div type="abstract" xml:lang="en">Abstract: 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.</div>
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<name sortKey="Terajima, Masanori" sort="Terajima, Masanori" uniqKey="Terajima M" first="Masanori" last="Terajima">Masanori Terajima</name>
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