Characterization of the attenuating M and NP gene segments of the avian influenza A/Mallard/78 virus during in vitro production of avian-human reassortant vaccine viruses and after replication in humans and primates
Identifieur interne : 002033 ( Main/Exploration ); précédent : 002032; suivant : 002034Characterization of the attenuating M and NP gene segments of the avian influenza A/Mallard/78 virus during in vitro production of avian-human reassortant vaccine viruses and after replication in humans and primates
Auteurs : John J. Treanor [États-Unis] ; Eveline L. Tierney [États-Unis] ; William T. London [États-Unis] ; Brian R. Murphy [États-Unis]Source :
- Vaccine [ 0264-410X ] ; 1991.
English descriptors
- Teeft :
- Amino, Amino acid sequences, Attenuated, Attenuated influenza reassortants, Attenuating, Attenuating genes, Attenuation, Attenuation phenotype, Avian, Avian influenza, Avian influenza virus, Avian virus, Backcross mating, Children vaccinated, Clone, Gene, Gene reassortants, Gene segment, Gene segments, Human influenza, Human influenza virus, Human virus, Influenza, Influenza reassortant virus, Influenza reassortant viruses, Influenza virus, Mutation, Nucleoprotein, Nucleotide, Nucleotide changes, Nucleotide sequence, Nucleotide sequence analysis, Nucleotide sequence changes, Nucleotide sequences, Other gene segments, Other genes, Parent virus, Phenotype, Polymerase, Reassortant, Reassortant vaccine viruses, Reassortant virus, Reassortant viruses, Reassortants, Replication, Segment, Sequence changes, Serial passage, Serial passages, Seronegative, Seronegative children, Single gene, Single gene reassortant viruses, Single nucleotide change, Squirrel, Squirrel monkeys, Tierney, Treanor, Unpassaged, Vaccine, Vaccine viruses, Viral, Virus, Virus reassortants, Virus replication, Virus vaccine, Vivo replication.
Abstract
Abstract: A unique requirement for live attenuated reassortant influenza vaccines is the need to generate new reassortant vaccine viruses with the appearance of each new antigenic variant. Thus, the attenuation phenotype conferred by the attenuated donor influenza virus must remain genetically stable during the generation of each new reassortant vaccine virus. In this study we used nucleotide sequence analysis to evaluate the genetic stability of the attenuating M and NP genes of the avian influenza A/Mallard/NY/6750/78 attenuated donor virus during the in vitro generation and subsequent in vivo replication of avian-human (AH) influenza A reassortant vaccine viruses in monkeys and humans. Nucleotide sequence changes in the M and NP genes occurred at a rate of ≈0.61 substitutions/1000 nt/reassortant during in vitro generation of four AH reassortant viruses. Only two nucleotide sequence changes occurred in the M and NP gene segments of four isolates of HINI or H3N2 AH vaccine viruses following 6–8 days of replication in seronegative children, and neither change affected amino acids previously identified as playing a potential role in attenuation. In addition, there were no changes in the nucleotide sequence of the M and NP genes of single gene AH reassortant viruses following five serial passages in squirrel monkeys. Finally, there was no change in the level or duration of replication of the single gene reassortant viruses in the upper or lower respiratory tract of monkeys following serial passage. These results suggest that nucleotide sequence changes occur infrequently during the production of reassortant influenza A vaccine viruses and their subsequent replication in humans and monkeys, and that genetic instability does not appear to represent a significant obstacle to this approach for production of live attenuated vaccines.
Url:
DOI: 10.1016/0264-410X(91)90035-5
Affiliations:
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Thus, the attenuation phenotype conferred by the attenuated donor influenza virus must remain genetically stable during the generation of each new reassortant vaccine virus. In this study we used nucleotide sequence analysis to evaluate the genetic stability of the attenuating M and NP genes of the avian influenza A/Mallard/NY/6750/78 attenuated donor virus during the in vitro generation and subsequent in vivo replication of avian-human (AH) influenza A reassortant vaccine viruses in monkeys and humans. Nucleotide sequence changes in the M and NP genes occurred at a rate of ≈0.61 substitutions/1000 nt/reassortant during in vitro generation of four AH reassortant viruses. Only two nucleotide sequence changes occurred in the M and NP gene segments of four isolates of HINI or H3N2 AH vaccine viruses following 6–8 days of replication in seronegative children, and neither change affected amino acids previously identified as playing a potential role in attenuation. In addition, there were no changes in the nucleotide sequence of the M and NP genes of single gene AH reassortant viruses following five serial passages in squirrel monkeys. Finally, there was no change in the level or duration of replication of the single gene reassortant viruses in the upper or lower respiratory tract of monkeys following serial passage. These results suggest that nucleotide sequence changes occur infrequently during the production of reassortant influenza A vaccine viruses and their subsequent replication in humans and monkeys, and that genetic instability does not appear to represent a significant obstacle to this approach for production of live attenuated vaccines.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Treanor, John J" sort="Treanor, John J" uniqKey="Treanor J" first="John J." last="Treanor">John J. Treanor</name></region><name sortKey="London, William T" sort="London, William T" uniqKey="London W" first="William T." last="London">William T. London</name><name sortKey="Murphy, Brian R" sort="Murphy, Brian R" uniqKey="Murphy B" first="Brian R." last="Murphy">Brian R. Murphy</name><name sortKey="Tierney, Eveline L" sort="Tierney, Eveline L" uniqKey="Tierney E" first="Eveline L." last="Tierney">Eveline L. Tierney</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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