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Article

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

Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
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Author to whom correspondence should be addressed.
Academic Editors: Emanuele Montomoli and Claudia Maria Trombetta
Vaccines 2021, 9(7), 800; https://doi.org/10.3390/vaccines9070800
Received: 29 May 2021 / Revised: 24 June 2021 / Accepted: 1 July 2021 / Published: 19 July 2021
(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)
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 an 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 to 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 passages 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. View Full-Text
Keywords: Influenza B; LAIV; PB1; vaccine stability Influenza B; LAIV; PB1; vaccine stability
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MDPI and ACS Style

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. https://doi.org/10.3390/vaccines9070800

AMA Style

Mo J, Cardenas-Garcia S, Santos JJS, Ferreri LM, Cáceres CJ, Geiger G, Perez DR, Rajao DS. Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine. Vaccines. 2021; 9(7):800. https://doi.org/10.3390/vaccines9070800

Chicago/Turabian Style

Mo, Jongsuk, Stivalis Cardenas-Garcia, Jefferson J. S. Santos, Lucas M. Ferreri, C. Joaquín Cáceres, Ginger Geiger, Daniel R. Perez, and Daniela S. Rajao. 2021. "Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine" Vaccines 9, no. 7: 800. https://doi.org/10.3390/vaccines9070800

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