Objective
Influenza (Flu) virus infections lead to thousands of deaths annually worldwide and billions of dollars of economic burden. Vaccination is the primary strategy for Flu prevention; however, effective protection requires a perfect match with the seasonal circulating strains. Seasonal vaccines target the hemagglutinin (HA) and neuraminidase (NA) proteins of the two predominant A and one B circulating strains, and induce high neutralizing antibody titers. Emerging Flu viruses escape host immunity by modifying HA glycosylation and masking the immunodominant epitopes of previous years’ strains. In consequence, yearly seasonal Flu vaccines have to be developed. Therefore, there is a need for a universal Flu vaccine that would protect against most variants.
Patterns of HA glycosylation show that there are only 5 – 6 alterations in a century of evolution, reflecting the limited possibilities for the virus to escape host immunity while retaining its infectivity. Therefore, by developing a vaccine that includes most relevant past seasonal (H1, H3, and B) and pandemic (H5, H7) strains, it might be feasible to develop a universal Flu vaccine.
The project will combine HA selection with the novel self-amplifying mRNA (SAM®) vaccine technology, which consists of a synthetic RNA delivered by lipid nanoparticles, and already proved immunogenic in mice with Flu H1 and H7. We will design five SAM(HA) vectors encoding combinations of four HA, prioritized to cover up to 20 relevant strains, and characterize their immunogenicity in mice by measuring hemagglutination-inhibition and virus neutralization titers. In-depth characterization of germinal center B cells and follicular helper T cells will be performed by mass cytometry (CyTOF). Finally, HA-specific CD4 and CD8 T-cell cytokine and cytotoxic responses will be determined by mass cytometry for correlates of protection.
At the end of this proposal, the development of a universal Flu vaccine should be achieved.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesinfluenza
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- natural sciencesbiological sciencesgeneticsRNA
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback.
You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Topic(s)
Call for proposal
FP7-PEOPLE-2013-IEF
See other projects for this call
Funding Scheme
MC-IEF - Intra-European Fellowships (IEF)Coordinator
53100 Siena
Italy