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FluB-RAM and FluB-RANS: Genome Rearrangement as Safe and Efficacious Live Attenuated Influenza B Virus Vaccines

Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated...

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Autores principales: Cardenas-Garcia, Stivalis, Cáceres, C. Joaquín, Jain, Aarti, Geiger, Ginger, Mo, Jong-Suk, Jasinskas, Algimantas, Nakajima, Rie, Rajao, Daniela S., Davies, D. Huw, Perez, Daniel R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402576/
https://www.ncbi.nlm.nih.gov/pubmed/34452022
http://dx.doi.org/10.3390/vaccines9080897
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author Cardenas-Garcia, Stivalis
Cáceres, C. Joaquín
Jain, Aarti
Geiger, Ginger
Mo, Jong-Suk
Jasinskas, Algimantas
Nakajima, Rie
Rajao, Daniela S.
Davies, D. Huw
Perez, Daniel R.
author_facet Cardenas-Garcia, Stivalis
Cáceres, C. Joaquín
Jain, Aarti
Geiger, Ginger
Mo, Jong-Suk
Jasinskas, Algimantas
Nakajima, Rie
Rajao, Daniela S.
Davies, D. Huw
Perez, Daniel R.
author_sort Cardenas-Garcia, Stivalis
collection PubMed
description Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated influenza virus vaccines (LAIVs) are thought to induce both humoral and cellular immune responses by mimicking a natural infection, but their effectiveness has recently come into question. Thus, the opportunity exists to find alternative approaches to improve overall influenza vaccine effectiveness. Two alternative IBV backbones were developed with rearranged genomes, rearranged M (FluB-RAM) and a rearranged NS (FluB-RANS). Both rearranged viruses showed temperature sensitivity in vitro compared with the WT type B/Bris strain, were genetically stable over multiple passages in embryonated chicken eggs and were attenuated in vivo in mice. In a prime-boost regime in naïve mice, both rearranged viruses induced antibodies against HA with hemagglutination inhibition titers considered of protective value. In addition, antibodies against NA and NP were readily detected with potential protective value. Upon lethal IBV challenge, mice previously vaccinated with either FluB-RAM or FluB-RANS were completely protected against clinical disease and mortality. In conclusion, genome re-arrangement renders efficacious LAIV candidates to protect mice against IBV.
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spelling pubmed-84025762021-08-29 FluB-RAM and FluB-RANS: Genome Rearrangement as Safe and Efficacious Live Attenuated Influenza B Virus Vaccines Cardenas-Garcia, Stivalis Cáceres, C. Joaquín Jain, Aarti Geiger, Ginger Mo, Jong-Suk Jasinskas, Algimantas Nakajima, Rie Rajao, Daniela S. Davies, D. Huw Perez, Daniel R. Vaccines (Basel) Article Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated influenza virus vaccines (LAIVs) are thought to induce both humoral and cellular immune responses by mimicking a natural infection, but their effectiveness has recently come into question. Thus, the opportunity exists to find alternative approaches to improve overall influenza vaccine effectiveness. Two alternative IBV backbones were developed with rearranged genomes, rearranged M (FluB-RAM) and a rearranged NS (FluB-RANS). Both rearranged viruses showed temperature sensitivity in vitro compared with the WT type B/Bris strain, were genetically stable over multiple passages in embryonated chicken eggs and were attenuated in vivo in mice. In a prime-boost regime in naïve mice, both rearranged viruses induced antibodies against HA with hemagglutination inhibition titers considered of protective value. In addition, antibodies against NA and NP were readily detected with potential protective value. Upon lethal IBV challenge, mice previously vaccinated with either FluB-RAM or FluB-RANS were completely protected against clinical disease and mortality. In conclusion, genome re-arrangement renders efficacious LAIV candidates to protect mice against IBV. MDPI 2021-08-12 /pmc/articles/PMC8402576/ /pubmed/34452022 http://dx.doi.org/10.3390/vaccines9080897 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cardenas-Garcia, Stivalis
Cáceres, C. Joaquín
Jain, Aarti
Geiger, Ginger
Mo, Jong-Suk
Jasinskas, Algimantas
Nakajima, Rie
Rajao, Daniela S.
Davies, D. Huw
Perez, Daniel R.
FluB-RAM and FluB-RANS: Genome Rearrangement as Safe and Efficacious Live Attenuated Influenza B Virus Vaccines
title FluB-RAM and FluB-RANS: Genome Rearrangement as Safe and Efficacious Live Attenuated Influenza B Virus Vaccines
title_full FluB-RAM and FluB-RANS: Genome Rearrangement as Safe and Efficacious Live Attenuated Influenza B Virus Vaccines
title_fullStr FluB-RAM and FluB-RANS: Genome Rearrangement as Safe and Efficacious Live Attenuated Influenza B Virus Vaccines
title_full_unstemmed FluB-RAM and FluB-RANS: Genome Rearrangement as Safe and Efficacious Live Attenuated Influenza B Virus Vaccines
title_short FluB-RAM and FluB-RANS: Genome Rearrangement as Safe and Efficacious Live Attenuated Influenza B Virus Vaccines
title_sort flub-ram and flub-rans: genome rearrangement as safe and efficacious live attenuated influenza b virus vaccines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402576/
https://www.ncbi.nlm.nih.gov/pubmed/34452022
http://dx.doi.org/10.3390/vaccines9080897
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