Community Research and Development Information Service - CORDIS

RNA-based influenza vaccine

Continuous efforts to develop an effective vaccine against influenza led European scientists to combine viral RNA with nanoparticles. Certain advantages of this novel system render it extremely promising.
RNA-based influenza vaccine
Influenza virus has an inherent capacity to mutate and switch subtypes every year. Annual flu epidemics highlight the inefficiency of current influenza vaccines. A synthetic vaccine readily adaptable to induce protection against any influenza subtype might be the answer.

The scope of the EU-funded REPLIXCEL (Highly efficient new generation synthetic RNA-replicon based vaccine) project was to develop RNA-based vaccines against the influenza virus. REPLIXCEL comprised two small medium enterprises and two academic institutions, which transferred knowledge and expertise. The vaccine design comprised RNA-based constructs loaded in nanoparticle vehicles for delivery to dendritic cells.

RNA replicons exhibited the capacity to replicate in the cytoplasm in a non-infective manner and translate into proteins. By generating multiple copies, RNA replicons increased the antigen load beyond that achieved with conventional vaccines. This closely mimicked events occurring in a virus infection and induced both humoral and cell-mediated immune responses.

REPLIXCEL constructs encoded influenza virus antigens (hemagglutinin H5 subtype and nucleoprotein) alongside luciferase to facilitate the analysis of targeting to dendritic cells. Researchers functionalised the nanoparticles with ligands to enhance dendritic cell targeting. They also used lipopeptide-based adjuvants to activate co-stimulatory molecules on dendritic cells and improve antigen presentation. Furthermore, for efficient RNA release within cells, the nanoparticle vehicles contained cationic groups. In vivo administration of the REPLIXCEL vaccine induced specific immune responses against influenza hemagglutinin and nucleoprotein.

The success of REPLIXCEL led to an FP7-funded project (UNIVAX), which aims at the pre-clinical development of the RNA-based vaccines. Considering the improved protection achieved against influenza and the capacity to work as a single-shot vaccine, a pan-influenza efficacious vaccine could be just round the corner.

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RNA, influenza, vaccine, nanoparticles, dendritic cells
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