Abstract

The widespread influenza virus infection further emphasizes the need for novel vaccine strategies that effectively reduce the impact of epidemic as well as pandemic influenza. Conventional influenza vaccines generally induce virus neutralizing antibody responses which are specific for a few antigenically related strains within the same subtype. However, antibodies directed against the conserved stalk domain of HA could neutralize multiple subtypes of influenza virus and thus provide broad-spectrum protection. In this study, we designed and constructed a recombinant baculovirus-based vaccine, rBac-HA virus, that expresses full-length HA of pandemic H1N1 influenza virus (A/California/04/09) on the viral envelope. We demonstrated that repeated intranasal immunizations with rBac-HA virus induced HA stalk-specific antibody responses and protective immunity against homologous as well as heterosubtypic virus challenge. The adoptive transfer experiment shows that the cross-protection is conferred by the immune sera which contain HA stalk-specific antibodies. These results warrant further development of rBac-HA virus as a broad-protective vaccine against influenza. The vaccine induced protection against infection with the same subtype as well as different subtype, promising a potential universal vaccine for broad protection against different subtypes to control influenza outbreaks including pandemic.

Highlights

  • Influenza virus is a major respiratory pathogen that causes annual outbreaks and occasional pandemics

  • In order to determine the expression level of HA on the baculovirus envelope, Spodoptera frugiperda 9 (Sf9) cells were infected with recombinant baculovirus displaying HA (rBac-HA) virus or Bac-control in 6 well plates at 10 MOI. 48 h post infection, the cells were harvested, washed two times with FACS buffer (0.5% fetal bovine serum (FBS), 0.09% NaN3 in PBS) and blocked with anti-mouse CD16/CD32 (Mouse BD Fc block; BD Pharmingen, San Diego, CA) for 5 min at room temperature

  • To further confirm the display of HA protein on the cell surface, Sf9 cells were infected with rBac-HA virus and 48 h later the cells were analyzed by flow cytometry following surface staining with HA-specific Abs

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Summary

Introduction

Influenza virus is a major respiratory pathogen that causes annual outbreaks and occasional pandemics. Vaccination against influenza is effective way to control the pathogen spread [1]. Production of current licensed influenza vaccines is based on growth of viruses in embryonated chicken eggs that could be problems when there is a high demand for fertilized eggs and risk of egg-related allergy reactions [2]. To prevent accelerating spread of influenza virus, several novel strategies are considered to overcome the egg-dependent production of influenza vaccines. Those include culture-based production of inactivated influenza vaccines [3], PLOS ONE | DOI:10.1371/journal.pone.0152485. Those include culture-based production of inactivated influenza vaccines [3], PLOS ONE | DOI:10.1371/journal.pone.0152485 March 29, 2016

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