tetano
Editor, Senior Moderator
J Virol. 2018 Aug 22. pii: JVI.01025-18. doi: 10.1128/JVI.01025-18. [Epub ahead of print]
[h=1]An alternative strategy as a quadrivalent live attenuated influenza virus vaccine.[/h] Wan Z[SUP]1[/SUP], Cardenas Garcia S[SUP]1[/SUP], Liu J[SUP]1[/SUP], Santos J[SUP]1[/SUP], Carnaccini S[SUP]1[/SUP], Geiger G[SUP]1[/SUP], Ferreri L[SUP]1[/SUP], Rajao D[SUP]1[/SUP], Perez DR[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus infections continue to pose a major public health threat worldwide associated with seasonal epidemics and sporadic pandemics. Vaccination is considered the first line of defense against influenza. Live attenuated influenza virus (LAIV) vaccines may provide superior responses compared to inactivated vaccines because the former can better elicit a combination of humoral and cellular responses by mimicking a natural infection. Unfortunately, during the 2013-2014, 2014-2015 and 2015-2016 seasons, concerns emerged about the effectiveness of the only LAIV approved in the U.S. that prevented the Advisory Committee on Immunization Practices (ACIP) from recommending its use. Such drawback opens up the opportunity for alternative LAIV strategies that could overcome such concerns. Previously, we developed a combined strategy of temperature sensitive mutations in the PB2 and PB1 segments and an epitope tag in the C-terminus of PB1 that effectively attenuates influenza A viruses of avian and mammalian origin. More recently, we adopted a similar strategy for influenza B viruses. The resulting attenuated (att) influenza A and B viruses were safe, immunogenic, and protective against lethal influenza virus challenge in a variety of animal models. In this report, we provide evidence of the potential use of our att strategy in a quadrivalent LAIV (QIV) formulation carrying H3N2 and H1N1 influenza A virus subtype viruses and two antigenic lineages of influenza B viruses. In na?ve, DBA/2J mice, two doses of the QIV elicited HI responses ≥40 and effectively protected against lethal challenge with prototypical pandemic H1N1 influenza A and influenza B virus strains.IMPORTANCE Seasonal influenza viruses infect 1 billion people worldwide, and it is associated to ∼500,000 deaths annually. In addition, the never-ending emergence of zoonotic influenza viruses associated with lethal human infections and pandemic concern calls for the development of better vaccines and/or vaccination strategies against influenza. Regardless of the strategy, novel influenza vaccines must aim at providing protection against both seasonal influenza A and B viruses. In this study, we tested an alternative quadrivalent live attenuated influenza virus vaccine (QIV) formulation whose individual components have been previously shown to provide protection. We demonstrate in proof-of principle studies in mice that the QIV provides effective protection against lethal challenge with either influenza A or B virus.
PMID: 30135124 DOI: 10.1128/JVI.01025-18
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[h=1]An alternative strategy as a quadrivalent live attenuated influenza virus vaccine.[/h] Wan Z[SUP]1[/SUP], Cardenas Garcia S[SUP]1[/SUP], Liu J[SUP]1[/SUP], Santos J[SUP]1[/SUP], Carnaccini S[SUP]1[/SUP], Geiger G[SUP]1[/SUP], Ferreri L[SUP]1[/SUP], Rajao D[SUP]1[/SUP], Perez DR[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus infections continue to pose a major public health threat worldwide associated with seasonal epidemics and sporadic pandemics. Vaccination is considered the first line of defense against influenza. Live attenuated influenza virus (LAIV) vaccines may provide superior responses compared to inactivated vaccines because the former can better elicit a combination of humoral and cellular responses by mimicking a natural infection. Unfortunately, during the 2013-2014, 2014-2015 and 2015-2016 seasons, concerns emerged about the effectiveness of the only LAIV approved in the U.S. that prevented the Advisory Committee on Immunization Practices (ACIP) from recommending its use. Such drawback opens up the opportunity for alternative LAIV strategies that could overcome such concerns. Previously, we developed a combined strategy of temperature sensitive mutations in the PB2 and PB1 segments and an epitope tag in the C-terminus of PB1 that effectively attenuates influenza A viruses of avian and mammalian origin. More recently, we adopted a similar strategy for influenza B viruses. The resulting attenuated (att) influenza A and B viruses were safe, immunogenic, and protective against lethal influenza virus challenge in a variety of animal models. In this report, we provide evidence of the potential use of our att strategy in a quadrivalent LAIV (QIV) formulation carrying H3N2 and H1N1 influenza A virus subtype viruses and two antigenic lineages of influenza B viruses. In na?ve, DBA/2J mice, two doses of the QIV elicited HI responses ≥40 and effectively protected against lethal challenge with prototypical pandemic H1N1 influenza A and influenza B virus strains.IMPORTANCE Seasonal influenza viruses infect 1 billion people worldwide, and it is associated to ∼500,000 deaths annually. In addition, the never-ending emergence of zoonotic influenza viruses associated with lethal human infections and pandemic concern calls for the development of better vaccines and/or vaccination strategies against influenza. Regardless of the strategy, novel influenza vaccines must aim at providing protection against both seasonal influenza A and B viruses. In this study, we tested an alternative quadrivalent live attenuated influenza virus vaccine (QIV) formulation whose individual components have been previously shown to provide protection. We demonstrate in proof-of principle studies in mice that the QIV provides effective protection against lethal challenge with either influenza A or B virus.
PMID: 30135124 DOI: 10.1128/JVI.01025-18
Free full text