Objective There is a threat that evolutionary responses can render vaccines ineffective, as illustrated by the emergence of the increasingly virulent Marek Disease Virus strains in poultry following vaccination campaigns. Assessing the ‘evolution-proof’ nature of vaccines targeting human viruses is challenging because it requires an understanding of the epidemiology, the within-host ecology and the evolutionary potential of the virus. To date, most investigations into the spread of vaccine-resistant strains are theoretical and are rarely constrained by data.We propose a novel alliance between evolutionary ecology and clinical research to assess the risk of vaccines selecting for resistant or virulent strains. Human papillomaviruses (HPV) and their vaccines provide an ideal study system. However, the scope of the project is wider and encompasses other DNA viruses. The project is divided into three parts. In Part A, we will decipher HPV within-host dynamics in genital infections. By combining mathematical modelling and longitudinal patient data, we will be able to parameterise within-host models and compare them. In Part B, we will jointly analyse host, virus and genital microbiota diversity using a community ecology approach to understand the infectious process. These results will be integrated into evolutionary epidemiology models allowing for diverse infections. In Part C, we will estimate virus substitution rates and use the results from Parts 1 and 2 to develop a multilevel analysis of HPV evolution in response to vaccination. We will also tackle more general questions related to the evolution of the virulence of human oncoviruses.A major asset of the project is the collection of clinical data in order to address a major public health issue using ideas and methods from evolutionary ecology. This will set a new agenda for the study of human viral infections and establish a perennial leading research group in Europe. Fields of science medical and health scienceshealth sciencespublic healthepidemiologymedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health scienceshealth sciencesinfectious diseasesDNA viruses Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2014 - ERC Consolidator Grant Call for proposal ERC-2014-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Net EU contribution € 1 485 731,71 Address Rue michel ange 3 75794 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS France Net EU contribution € 1 485 731,71 Address Rue michel ange 3 75794 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 CENTRE HOSPITALIER UNIVERSITAIRE MONTPELLIER France Net EU contribution € 501 761,25 Address Avenue du doyen gaston giraud 191 34000 Montpellier See on map Region Occitanie Languedoc-Roussillon Hérault Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00