Development of an alternative modified live influenza B virus vaccine

Jefferson J.S. Santos, Courtney Finch, Troy Sutton, Adebimpe Obadan, Isabel Aguirre, Zhimin Wan, Diego Lopez, Ginger Geiger, Ana Silvia Gonzalez-Reiche, Lucas Ferreri, Daniel R. Perez

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Influenza B virus (IBV) is considered a major human pathogen, responsible for seasonal epidemics of acute respiratory illness. Two antigenically distinct IBV hemagglutinin (HA) lineages cocirculate worldwide with little cross-reactivity. Live attenuated influenza virus (LAIV) vaccines have been shown to provide better crossprotective immune responses than inactivated vaccines by eliciting local mucosal immunity and systemic B cell- and T cell-mediated memory responses. We have shown previously that incorporation of temperature-sensitive (ts) mutations into the PB1 and PB2 subunits along with a modified HA epitope tag in the C terminus of PB1 resulted in influenza A viruses (IAV) that are safe and effective as modified live attenuated (att) virus vaccines (IAV att). We explored whether analogous mutations in the IBV polymerase subunits would result in a stable virus with an att phenotype. The PB1 subunit of the influenza B/Brisbane/60/2008 strain was used to incorporate ts mutations and a C-terminal HA tag. Such modifications resulted in a B/Bris att strain with ts characteristics in vitro and an att phenotype in vivo. Vaccination studies in mice showed that a single dose of the B/Bris att candidate stimulated sterilizing immunity against lethal homologous challenge and complete protection against heterologous challenge. These studies show the potential of an alternative LAIV platform for the development of IBV vaccines.

Original languageEnglish (US)
Article numbere00056-17
JournalJournal of virology
Volume91
Issue number12
DOIs
StatePublished - Jun 1 2017

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Influenza B virus
Influenza Vaccines
Hemagglutinins
hemagglutinins
vaccines
Attenuated Vaccines
Influenza A virus
Orthomyxoviridae
mutation
Mutation
Temperature
Viruses
Phenotype
mucosal immunity
phenotype
Mucosal Immunity
viruses
temperature
Inactivated Vaccines
inactivated vaccines

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Santos, J. J. S., Finch, C., Sutton, T., Obadan, A., Aguirre, I., Wan, Z., ... Perez, D. R. (2017). Development of an alternative modified live influenza B virus vaccine. Journal of virology, 91(12), [e00056-17]. https://doi.org/10.1128/JVI.00056-17
Santos, Jefferson J.S. ; Finch, Courtney ; Sutton, Troy ; Obadan, Adebimpe ; Aguirre, Isabel ; Wan, Zhimin ; Lopez, Diego ; Geiger, Ginger ; Gonzalez-Reiche, Ana Silvia ; Ferreri, Lucas ; Perez, Daniel R. / Development of an alternative modified live influenza B virus vaccine. In: Journal of virology. 2017 ; Vol. 91, No. 12.
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abstract = "Influenza B virus (IBV) is considered a major human pathogen, responsible for seasonal epidemics of acute respiratory illness. Two antigenically distinct IBV hemagglutinin (HA) lineages cocirculate worldwide with little cross-reactivity. Live attenuated influenza virus (LAIV) vaccines have been shown to provide better crossprotective immune responses than inactivated vaccines by eliciting local mucosal immunity and systemic B cell- and T cell-mediated memory responses. We have shown previously that incorporation of temperature-sensitive (ts) mutations into the PB1 and PB2 subunits along with a modified HA epitope tag in the C terminus of PB1 resulted in influenza A viruses (IAV) that are safe and effective as modified live attenuated (att) virus vaccines (IAV att). We explored whether analogous mutations in the IBV polymerase subunits would result in a stable virus with an att phenotype. The PB1 subunit of the influenza B/Brisbane/60/2008 strain was used to incorporate ts mutations and a C-terminal HA tag. Such modifications resulted in a B/Bris att strain with ts characteristics in vitro and an att phenotype in vivo. Vaccination studies in mice showed that a single dose of the B/Bris att candidate stimulated sterilizing immunity against lethal homologous challenge and complete protection against heterologous challenge. These studies show the potential of an alternative LAIV platform for the development of IBV vaccines.",
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Santos, JJS, Finch, C, Sutton, T, Obadan, A, Aguirre, I, Wan, Z, Lopez, D, Geiger, G, Gonzalez-Reiche, AS, Ferreri, L & Perez, DR 2017, 'Development of an alternative modified live influenza B virus vaccine', Journal of virology, vol. 91, no. 12, e00056-17. https://doi.org/10.1128/JVI.00056-17

Development of an alternative modified live influenza B virus vaccine. / Santos, Jefferson J.S.; Finch, Courtney; Sutton, Troy; Obadan, Adebimpe; Aguirre, Isabel; Wan, Zhimin; Lopez, Diego; Geiger, Ginger; Gonzalez-Reiche, Ana Silvia; Ferreri, Lucas; Perez, Daniel R.

In: Journal of virology, Vol. 91, No. 12, e00056-17, 01.06.2017.

Research output: Contribution to journalArticle

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AU - Santos, Jefferson J.S.

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AU - Sutton, Troy

AU - Obadan, Adebimpe

AU - Aguirre, Isabel

AU - Wan, Zhimin

AU - Lopez, Diego

AU - Geiger, Ginger

AU - Gonzalez-Reiche, Ana Silvia

AU - Ferreri, Lucas

AU - Perez, Daniel R.

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