A New Master Donor Virus for the Development of Live-Attenuated Influenza B Virus Vaccines.

Chantelle L White,Luis Martínez-Sobrido,Jefferson Santos,Daniel R Perez,Kevin Chiem,Aitor Nogales,Stivalis Cardenas Garcia

doi:10.3390/v13071278

Abstract

Influenza B viruses (IBV) circulate annually, with young children, the elderly and immunocompromised individuals being at high risk. Yearly vaccinations are recommended to protect against seasonally influenza viruses, including IBV. Live attenuated influenza vaccines (LAIV) provide the unique opportunity for direct exposure to the antigenically variable surface glycoproteins as well as the more conserved internal components. Ideally, LAIV Master Donor Viruses (MDV) should accurately reflect seasonal influenza strains. Unfortunately, the continuous evolution of IBV have led to significant changes in conserved epitopes compared to the IBV MDV based on B/Ann Arbor/1/1966 strain. Here, we propose a recent influenza B/Brisbane/60/2008 as an efficacious MDV alternative, as its internal viral proteins more accurately reflect those of circulating IBV strains. We introduced the mutations responsible for the temperature sensitive (ts), cold adapted (ca) and attenuated (att) phenotype of B/Ann Arbor/1/1966 MDV LAIV into B/Brisbane/60/2008 to generate a new MDV LAIV. In vitro and in vivo analysis demonstrated that the mutations responsible of the ts, ca, and att phenotype of B/Ann Arbor/1/1966 MDV LAIV were able to infer the same phenotype to B/Brisbane/60/2008, demonstrating its potential as a new MDV for the development of LAIV to protect against contemporary IBV strains.

Highlights

Over the last century, influenza viruses have been responsible of both yearly seasonal and occasional pandemics infections of great consequences to humans
H2N2 PB1, together with an HA epitope tag in the C terminus of Influenza B viruses (IBV) PB1, were able to confer a ts phenotype in vitro and an att phenotype in vivo to B/Brisbane/60/2008, while protecting against challenge with IBV [70]. In this manuscript we evaluated whether the ts, ca and att mutations present in IBV Master Donor Viruses (MDV) Live attenuated influenza vaccines (LAIV) B/Ann Arbor/1/1966 would be able to confer the same phenotype to a most recent B/Brisbane/60/2008 strain and, importantly, if this new IBV MDV LAIV
B/Brisbane/60/2008 was selected as the potential MDV LAIV candidate because this Victoria lineage IBV circulated more recently (2008) within the human population and because its internal genes have increased percent identity and sequence homology with contemporary IBV strains circulating in humans, relatively to the current B/Ann

Summary

Introduction

Influenza viruses have been responsible of both yearly seasonal and occasional pandemics infections of great consequences to humans. A viruses (IAV) circulate within several zoonotic hosts, providing the opportunity for pandemic, Influenza B viruses (IBV) primarily circulate in humans, and are not considered a pandemic threat. IBV are still major human pathogens responsible for seasonal epidemics of respiratory illness [1,2,3]. Similar to IAV, IBV are enveloped negative-sense, single-stranded segmented RNA viruses that belong to the Orthomyxoviridae family [13,14,15]. Hemagglutinin (HA) and Neuraminidase (NA) are the two major glycoproteins and antigenic determinants in the surface of IBV; and responsible for viral entry and fusion (HA), and release from infected cells (NA) [14,15,16].

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Results

Conclusion