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Genetic Basis of Attenuation of Cold-Adapted Influenza Strain B/Leningrad/14/17/55 — Backup Master Donor Virus for Influenza Type B Live Attenuated Vaccines

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Bulletin of Experimental Biology and Medicine Aims and scope

The reassortant vaccine strain of live attenuated influenza vaccine inherits temperature sensitivity and areactogenicity from cold-adapted attenuated master donor virus. In Russia, B/ USSR/60/69 master donor virus (B60) is currently in use for the preparation of live attenuated type B influenza vaccine candidates. Trivalent live attenuated influenza vaccine based on A/ Leningrad/134/17/57 and B60 are licensed for the use in Russia for single dose vaccination of adults and children over 3 years. B/Leningrad/14/17/55 (B14) cold-adapted virus is a backup master donor virus for live attenuated type B influenza vaccine. According to our preliminary estimates, it is more attenuated than B60, which can allow expanding applicability of this vaccine for children under 3 years of age. In this paper, the role of B14 genes in its attenuation was assessed. Representative collection of reassortants of B14 with epidemic influenza B viruses was obtained, a phenotypic analysis of reassortants was performed, and their pathogenicity for animals was assessed. The leading role of PB2 and PA genes in attenuation of B14 master donor virus was proven.

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References

  1. Krutikova EV, Kiseleva IV, Fedorova EA, Dubrovina IA, Bol’shunova EA, Rudenko LG. Cold-adapted In/Leningrad/ 14/17/55 virus as an alternative master donor strain for live attenuated influenza vaccine for young children. Med. Akad. Zh. 2016;16(4):156-157. Russian.

  2. Ambrose CS, Levin MJ. The rationale for quadrivalent influenza vaccines. Hum. Vaccines Immunother. 2012;8(1):81-88.

    Article  Google Scholar 

  3. Hoffmann E, Mahmood K, Chen Z, Yang CF, Spaete J, Greenberg HB, Herlocher ML, Jin H, Kemble G. Multiple gene segments control the temperature sensitivity and attenuation phenotypes of ca B/Ann Arbor/1/66. J. Virol. 2005;79(17):11,014-11,021.

    Article  CAS  Google Scholar 

  4. Jin H, Lu B, Zhou H, Ma C, Zhao J, Yang CF, Kemble G, Greenberg H. Multiple amino acid residues confer temperature sensitivity to human influenza virus vaccine strains (Flu-Mist) derived from cold-adapted A/Ann Arbor/6/60. Virology. 2003;306(1):18-24.

    Article  CAS  Google Scholar 

  5. Kiseleva I, Klimov A, Su Q, Szymkowiak C, Toner T, Kwan WS, Rudenko L, Shaw AR, Youil R. Role of individual genes of the A/Leningrad/134/17/57 (H2N2) cold-adapted donor strain in manifestation of the temperature-sensitive phenotype of reassortant influenza A viruses. Int. Congress Series. 2004;1263:547-550.

    Article  CAS  Google Scholar 

  6. Kiseleva I, Larionova N, Rudenko L. Live attenuated reassortant vaccines based on A/Leningrad/134/17/57 master donor virus against H5 avian influenza. Open Microbiol. J. 2017;11:316-329.

    Article  CAS  Google Scholar 

  7. Kiseleva IV, Voeten JT, Teley LC, Larionova NV, Drieszenvan der Cruijsen SK, Basten SM, Heldens JG, van den Bosch H, Rudenko LG. PB2 and PA genes control the expression of the temperature-sensitive phenotype of cold-adapted B/ USSR/60/69 influenza master donor virus. J. Gen. Virol. 2010;9(Pt 4):931-937.

    Article  CAS  Google Scholar 

  8. Krutikova EV, Stepanova EA, Kiseleva IV, Rudenko LG. Express screening of reassortants of Influenza Virus B — candidates for vaccinating strains of live Influenza vaccine by using pyrosequencing. Mol. Gen. Microbiol. Virol. 2018;33(2):139- 144.

    Article  Google Scholar 

  9. Martínez-Sobrido L, Peersen O, Nogales A. Temperature sensitive mutations in influenza A viral ribonucleoprotein complex responsible for the attenuation of the live attenuated influenza vaccine. Viruses. 2018;10(10. pii: E560. doi: 10.3390/v10100560

  10. Rudenko L, Yeolekar L, Kiseleva I, Isakova-Sivak I. Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories. Vaccine. 2016;34(45):5436-5441.

    Article  Google Scholar 

  11. Stepanova EA, Krutikova EV, Kiseleva IV, Rudenko LG. The Spatial location of single amino acid substitutions in proteins of cold-adapted influenza B viruses and their impact upon cold adaptation. Mol. Genet. Microbiol. Virol. 2018;33(3):169-181.

    Article  Google Scholar 

  12. Wilk E, Schughart K. The mouse as model system to study host-pathogen interactions in influenza A infections. Curr. Protoc. Mouse Biol. 2012;2(2):177-205.

    Article  Google Scholar 

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Correspondence to E. V. Krutikova.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 168, No. 11, pp. 615-618, November, 2019

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Krutikova, E.V., Stepanova, E.A., Wong, P.F. et al. Genetic Basis of Attenuation of Cold-Adapted Influenza Strain B/Leningrad/14/17/55 — Backup Master Donor Virus for Influenza Type B Live Attenuated Vaccines. Bull Exp Biol Med 168, 669–672 (2020). https://doi.org/10.1007/s10517-020-04777-x

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  • DOI: https://doi.org/10.1007/s10517-020-04777-x

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