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dc.contributor.authorTerajima, Masanori
dc.contributor.authorJameson, Julie Marie
dc.contributor.authorNorman, Joyce E.
dc.contributor.authorCruz, John
dc.contributor.authorEnnis, Francis A.
dc.date2022-08-11T08:08:49.000
dc.date.accessioned2022-08-23T16:09:24Z
dc.date.available2022-08-23T16:09:24Z
dc.date.issued1999-06-12
dc.date.submitted2009-01-13
dc.identifier.citationVirology. 1999 Jun 20;259(1):135-40. <a href="http://dx.doi.org/10.1006/viro.1999.9719">Link to article on publisher's site</a>
dc.identifier.issn0042-6822 (Print)
dc.identifier.doi10.1006/viro.1999.9719
dc.identifier.pmid10364497
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32685
dc.description.abstractCurrent 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10364497&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1006/viro.1999.9719
dc.subjectBase Sequence; CD8-Positive T-Lymphocytes; Genes, Viral; HLA-A Antigens; Humans; Influenza Vaccines; Molecular Sequence Data; Mutation; Orthomyxoviridae; Reassortant Viruses; Viral Nonstructural Proteins
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleHigh-yield reassortant influenza vaccine production virus has a mutation at an HLA-A 2.1-restricted CD8+ CTL epitope on the NS1 protein
dc.typeJournal Article
dc.source.journaltitleVirology
dc.source.volume259
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1243
dc.identifier.contextkey693153
html.description.abstract<p>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.</p>
dc.identifier.submissionpathgsbs_sp/1243
dc.contributor.departmentCenter for Infectious Disease and Vaccine Research
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages135-40


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