FERFLU EXPRESS

Investigation of influenza immune responses and vaccine efficacy correlates by global expression profiling and immunological analyses in the ferret model of influenza

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 Obiettivo del progetto (Objective)

'Pandemic influenza, such as the 2009 H1N1 influenza virus strains that recently emerged in Mexico and in the US, can have serious effects on human health. Development of vaccines that are able to elicit more potent and protective immune responses as well as reducing the impact of future pandemic outbreaks is critical. Successful development of such vaccines is dependent on animal models to test vaccine efficacy and safety. Animal modeling of infectious disease also allows for transcription mapping of the cellular and molecular mechanisms by which these viruses infect as well as how the vaccines against them provide protection. We will use the ferret influenza model to build a comprehensive map the genes signatures involved at the different stages of the immune response to influenza virus infection. We will also analyze the transcriptional profiles induced by vaccination using standard inactivated and live attenuated influenza vaccine currently being administered to humans. In addition, we will study the gene expression responses triggered by virus challenge in vaccinated animals. Careful mapping of the gene responses triggered by influenza infection, as well as the mechanisms the virus use to overcome these responses will provide key information for development of vaccines and antiviral drugs against epidemic and pandemic influenza strains.'

Introduzione (Teaser)

A European study unveiled a number of genetic biomarkers associated with influenza infection. Prompt diagnosis using these biomarkers is expected to reduce viral spread.

Descrizione progetto (Article)

Influenza pandemics, such as the one caused by H1N1 viral strain in 2009 pose a global threat to human health. Although vaccination remains the cornerstone for prophylaxis against influenza virus infection, the need remains to obtain a deeper understanding on the triggered immune responses.

In this context, the EU-funded FERFLU EXPRESS project worked on the ferret model of influenza infection to closely monitor the immune response at the molecular level. For this purpose, researchers performed comparative gene expression analysis in infected versus immunised animals. Their aim was to identify key genetic biomarkers correlating with vaccine protection.

De-novo sequencing of the transcriptome from influenza infected ferrets unveiled more than 1 000 genes that were involved in the innate and adaptive immune response against influenza. Scientists also analysed the gene expression changes induced by closely related influenza strains. Although most gene expression changes followed a strain-specific pattern, a common set of genes was identified.

Additionally, they established sophisticated statistical algorithms to identify genes that could be used to predict the influenza strain and the associated lung pathology. The discovery of promising genetic biomarkers is expected to lead to the development of novel diagnostic tools for detecting highly pathogenic influenza strains.

Collectively, implementation of the FERFLU EXPRESS deliverables is expected to minimise transmission of virulent influenza strains and improve clinical outcome by initiating early treatment. Given the extensive socioeconomic impact of influenza pandemics, this may alleviate some of the burden imposed on healthcare systems across Europe.