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Live attenuated reassortant influenza vaccine prepared using A/Leningrad/134/17/57 (H2N2) donor strain is genetically stable after replication in children 3-6 years of age

Identifieur interne : 000654 ( Istex/Checkpoint ); précédent : 000653; suivant : 000655

Live attenuated reassortant influenza vaccine prepared using A/Leningrad/134/17/57 (H2N2) donor strain is genetically stable after replication in children 3-6 years of age

Auteurs : A. I. Klimov [États-Unis] ; I. V. Kiseleva [Russie] ; J. A. Desheva [Russie] ; G. I. Alexandrova [Russie] ; N. J. Cox [États-Unis] ; L. G. Rudenko [Russie]

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RBID : ISTEX:3C35F12C425DB52E73CF2BBCBAFA9416C1FB67A7

English descriptors

Abstract

Abstract: Background: Live influenza A vaccines (LIVs) for adults and children are prepared in Russia by reassorting current epidemic strains with cold-adapted (ca) attenuated donor viruses A/Leningrad/134/17/57 (H2N2) (Len/17) and A/Leningrad/134/47/57 (H2N2) (Len/47), respectively. Len/17 and Len/47 were derived from the A/Leningrad/134/57 (H2N2) wild-type virus after 17 and 47 passages in eggs at 25 °C. Two doses of Len/47-based vaccine have been used for vaccinating children. In a recent study, children were vaccinated with the Len/17-based LIV in order to determine if this vaccine is safe and immunogenic after a single dose vaccination. As part of this study, type A isolates obtained from children 3–6 years of age on the third day after vaccination were analyzed for genetic stability. Methods: PCR-restriction (RFLP) analysis was used to detect mutations in genomes of isolates. Results: Internal genes of Len/17 contain eight coding mutations in the PB2 (1), PB1 (2), PA (2), M1 (1), M2 (1) and NS (1) genes. All of these mutations, except one, were conserved in the genomes of all 28 strains studied. Similar to other studies with Len/17, the A-86-T change in the M2 protein, which was shown to be heterogeneous in the parent donor strain, was absent in 13 isolates. Since it was shown that mutations in polymerase genes play a leading role in the attenuation of Len/17, it is important to emphasize their conservation in all of the isolates. Moreover, an additional mutation in the PB2 protein (S-478-R), previously known only for the more attenuated Len/47 ca donor strain, was detected in 9 of 28 isolates, indicating that this mutation may also be heterogeneous in the donor virus. Conclusion: The Len/17-based LIV is genetically stable in children.

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DOI: 10.1016/S0531-5131(01)00020-6


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ISTEX:3C35F12C425DB52E73CF2BBCBAFA9416C1FB67A7

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<div type="abstract" xml:lang="en">Abstract: Background: Live influenza A vaccines (LIVs) for adults and children are prepared in Russia by reassorting current epidemic strains with cold-adapted (ca) attenuated donor viruses A/Leningrad/134/17/57 (H2N2) (Len/17) and A/Leningrad/134/47/57 (H2N2) (Len/47), respectively. Len/17 and Len/47 were derived from the A/Leningrad/134/57 (H2N2) wild-type virus after 17 and 47 passages in eggs at 25 °C. Two doses of Len/47-based vaccine have been used for vaccinating children. In a recent study, children were vaccinated with the Len/17-based LIV in order to determine if this vaccine is safe and immunogenic after a single dose vaccination. As part of this study, type A isolates obtained from children 3–6 years of age on the third day after vaccination were analyzed for genetic stability. Methods: PCR-restriction (RFLP) analysis was used to detect mutations in genomes of isolates. Results: Internal genes of Len/17 contain eight coding mutations in the PB2 (1), PB1 (2), PA (2), M1 (1), M2 (1) and NS (1) genes. All of these mutations, except one, were conserved in the genomes of all 28 strains studied. Similar to other studies with Len/17, the A-86-T change in the M2 protein, which was shown to be heterogeneous in the parent donor strain, was absent in 13 isolates. Since it was shown that mutations in polymerase genes play a leading role in the attenuation of Len/17, it is important to emphasize their conservation in all of the isolates. Moreover, an additional mutation in the PB2 protein (S-478-R), previously known only for the more attenuated Len/47 ca donor strain, was detected in 9 of 28 isolates, indicating that this mutation may also be heterogeneous in the donor virus. Conclusion: The Len/17-based LIV is genetically stable in children.</div>
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