Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine

Jongsuk Mo
,
Stivalis Cardenas-Garcia
ORCID logo ,
Jefferson J. S. Santos
,
Lucas M. Ferreri
,
C. Joaquín Cáceres
ORCID logo ,
Ginger Geiger
ORCID logo ,
Daniel R Perez
,
Daniela S. Rajao
* ORCID logo
Version 1 : Received: 9 June 2021 / Approved: 11 June 2021 / Online: 11 June 2021 (08:41:04 CEST)

A peer-reviewed article of this Preprint also exists.

Mo, J.; Cardenas-Garcia, S.; Santos, J.J.S.; Ferreri, L.M.; Cáceres, C.J.; Geiger, G.; Perez, D.R.; Rajao, D.S. Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine. Vaccines 2021, 9, 800. Mo, J.; Cardenas-Garcia, S.; Santos, J.J.S.; Ferreri, L.M.; Cáceres, C.J.; Geiger, G.; Perez, D.R.; Rajao, D.S. Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine. Vaccines 2021, 9, 800.

Abstract

Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of a HA epitope tag in the PB1 segment of B/Brisbane/60/2008 (B/Bris) resulted in an attenuated strain that was safe and effective as a live attenuated vaccine. A third attempted mutation (K391E) in PB1 was not always stable. Interestingly, viruses that maintained the K391E mutation were associated with the mutation E48K. To explore the contribution of the E48K mutation for stability of the K391E mutation, a vaccine candidate was generated by inserting both mutations along with attenuating mutations E580G and S660A in PB1 of B/Bris (B/Bris PB1att 4M). Serial passage of the B/Bris PB1att 4M vaccine candidate in eggs and MDCK indicated high stability. In silico structural analysis revealed a potential interaction between amino acids at positions 48 and 391. In mice, B/Bris PB1att 4M was safe and provided complete protection against homologous challenge. These results confirm the compensatory effect of mutation E48K to stabilize the K391E mutation, resulting in a safer, yet still protective, IBV LAIV vaccine.

Keywords

Influenza B; LAIV; PB1; vaccine stability

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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