Abstract

There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV) adjuvated with the saponin-based adjuvant Matrix-M (MM) can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

Highlights

  • Influenza is a negative strand RNA virus that can be classified into influenza A, B and C viruses

  • To investigate the immune potentiating properties of MM, mice were immunized once or twice with trivalent virosomal vaccine (TVV) or TVV combined with MM (TVV+MM)

  • A similar pattern of antibody responses were observed against vaccine homologous H3 demonstrating that immunizations with 1x or 2x TVV resulted in statistically significant induction of H3-spefific antibody titers as compared to the vehicle control group (PBS injected mice) (p

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Summary

Introduction

Influenza is a negative strand RNA virus that can be classified into influenza A, B and C viruses. While influenza B and C mainly infect humans, influenza A infects a broad range of hosts including humans, birds and pigs [1]. The influenza envelope contains two major glycoproteins, namely hemagglutinin (HA) and neuraminidase (NA). There is a constant threat of influenza A viruses crossing the species barrier and causing human pandemics such as the pandemic outbreaks of H1N1 in 1918, H2N2 in 1952, H3N2 in 1968 and again an H1N1 in 2009 [3, 4]. Descendants of the pandemic H3N2 and H1N1 strains of 1968 and 2009, respectively, and two influenza B strains circulate among humans and cause seasonal influenza epidemics [5]

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