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Titolo:
GENETICALLY-ENGINEERED LIVE ATTENUATED INFLUENZA-A VIRUS-VACCINE CANDIDATES
Autore:
PARKIN NT; CHIU P; COELINGH K;
Indirizzi:
VIROLOG,270 E GRAND AVE S SAN FRANCISCO CA 94080 AVIRON MT VIEW CA 94043
Titolo Testata:
Journal of virology
fascicolo: 4, volume: 71, anno: 1997,
pagine: 2772 - 2778
SICI:
0022-538X(1997)71:4<2772:GLAIVC>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
TEMPERATURE-SENSITIVE PHENOTYPE; POLYMERASE BASIC PROTEIN-2; VIRAL-RNA TRANSCRIPTION; CHRONICALLY ILL ADULTS; A VIRUS; P-PROTEINS; PB2 GENE; REASSORTANT VIRUSES; SEQUENCE CHANGES; MUTANT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
53
Recensione:
Indirizzi per estratti:
Citazione:
N.T. Parkin et al., "GENETICALLY-ENGINEERED LIVE ATTENUATED INFLUENZA-A VIRUS-VACCINE CANDIDATES", Journal of virology, 71(4), 1997, pp. 2772-2778

Abstract

We have generated new influenza A virus live attenuated vaccine candidates by site-directed mutagenesis and reverse genetics. By mutating specific amino acids in the PB2 polymerase subunit, two temperature-sensitive (ts) attenuated viruses were obtained, Both candidates have 38 degrees C shutoff temperatures in MDCK cells, are attenuated in the respiratory tracts of mice and ferrets, and have very low reactogenicityin ferrets. Infection of mice or ferrets with either mutant conferredsignificant protection from challenge with the homologous wild-type virus. Three tests for genetic stability were used to assess the propensity for reversion to virulence: 14 days of replication in nude mice, growth at 37 degrees C in tissue culture, and serial passage in ferrets. One candidate, which contains mutations intended to reduce the ability of PB2 to bind to cap structures, was stable in all three assays, whereas the second candidate, which contains mutations found only in other ts strains of influenza virus, lost its ts phenotype in the last two assays. This approach has therefore enabled the creation of live attenuated influenza A virus vaccine candidates suitable for human testing.

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Documento generato il 02/07/20 alle ore 18:42:10