The development of vaccines against COVID-19 and their global access are a priority to control and hopefully end the current worldwide pandemic [1]. However, the success of this strategy strongly relies on people’s trust in this immunization: What if people refuse the shot? This is not a rhetorical question: the most recent studies found that 37% of the French population would refuse the vaccine. The main reason for this refusal was the fear that the vaccine would not be safe and refusal was strongly correlated to political attitudes. The objective of this project is to monitor the French population’s attitudes toward a COVID-19 vaccine during the next year, until, and if possible, after it is made available, as well as their evolution and their determinants (including socioeconomic status, attitudes toward science and health authorities but also vaccine-critical mobilisations), with a focus on their potential politicization. We assume that hostile attitudes toward this vaccine may reflect VH in specific groups of people, while in other groups, they may be rooted in anti-vaccination and/or conspiracy feelings. Moreover we will monitor whether such attitudes remain associated to political views, especially to the extremes of the political game. We will mainly rely on repeated cross-sectional surveys conducted among the French general population. We plan to conduct five cross-sectional surveys among representative samples of the French adult (aged 18+) population according to the following design: first and last surveys with a quite long questionnaire in a sample of 2,000 participants, (months 0 & 12); three other surveys with a shorter questionnaire and a smaller sample (N=1,000; at months 3, 6 & 9). This original design is very likely to evolve, especially according to the epidemic and political context and the marketing of a future COVID-19 vaccine. We will combine these surveys with other data: another quantitative survey carried out among French GPs in the Fall of 2020 (n>3300) , the evolution of the public’s queries on Google between Fall 2020 and Fall 2021, and data collected on Twitter during the same period. The latter will enable to integrate the activist mobilizations that arise around the COVID-19 vaccine, how they politicize the vaccine and their respective capacity to reach a wide audience. This project will involve a consortium of researchers with great experience of working on vaccine hesitancy. Our proposal fits primarily in the theme of Ethics & social dynamics, and it deals more particularly with representations, perceptions, attitudes, behaviors related to the epidemic. Moreover, our project will produce relevant knowledge to design politics aiming at improving the population’s willingness to get immunized against the COVID-19 and propensity of GPs to recommend it (theme Infection prevention and control). Our project aims to combine operational objectives with longer-term scientific objectives. In the short term, the aim is to set up and make available to the authorities a monitoring of French population’s attitudes toward a vaccine against the COVID-19, as well as their determinants, in order to contribute to design strategies aiming at improving adherence to this vaccine, and to avoid the precedent of the vaccination campaign against H1N1 flu in 2009-2010. Regarding longer term scientific objectives, we expect this project will help us improve our knowledge and understanding of contemporary VH. Beyond VH, it will also contribute to the analysis of the contemporary shift toward the politicization of public health issues as well as the complexity of attitudes toward science.

The rapid advances in sequencing and computational technologies accompanied by a drastic reduction of sequencing costs have revolutionized microbial genomics and provided an unprecedented insight into microbial evolution, diversity, and host–pathogen interaction. Moreover, genomic technologies demonstrated great potential and suitability for clinical diagnostics or the real-time detection and surveillance of epidemics. The overall goal of the PREPMedVet partners (FLI, BNITM, ANSES, and AMU) is to set up a portable diagnostic sequencing platform capable to deliver in a clinically relevant turnaround time critical information in the context of an outbreak. The consortium has aimed to develop a standard wet-lab protocol which could be applied on-site using portable next-generation sequencing platforms and user-friendly sequence analysis software’s capable to deliver valuable insight into epidemic transmission patterns, pathogen genomics, evolution and the possible source of origin. The identification of pathogens will be flanked by production and validation of easy-to-use detection assays that can be stockpiled, transported, and delivered to the end users for timely and comprehensive reaction on outbreak scenarios. The project PREPMedVet combines French and German key partners relevant in Human and Animal Health in a One Health approach and integrates relevant multiplying end users from the field.

Human papillomavirus (HPV) infections cause various clinical conditions, especially cervical cancer, which is the leading cause of cancer deaths in sub-Saharan Africa, including Senegal, where a national HPV vaccine campaign targeting girls aged 9 is currently deployed. This campaign is conducted in a context characterized by the rise of vaccine hesitancy (VH), which includes, among other things, trust issues among the population regarding the safety and efficacy of vaccines, but also the rise of vaccine-specific attitudes and behaviors. Our project aims at a better understanding of lay people’s and health workers’ beliefs, attitudes and behaviors toward vaccination issues in this context. We will target both rural and urban areas, but specifically in the South of Senegal, where immunization rates for childhood vaccines are the lowest in the country. Four objectives structure our project, resulting in 8 different Work Packages. As regards the issue of identifying the actors involved in HPV vaccination decision, and then understanding their respective roles, a first WP will consist in a review of the scientific and grey literature related to vaccination-related beliefs, attitudes and behaviors in sub-Saharan Africa. In addition, 3 other WP are planned corresponding to three series of in-depth interviews, targeting respectively mothers (WP2), other lay people possibly involved in decision-making about HPV (WP3), and health workers involved in the HPV immunization campaign (WP4). Another main issue of the project is about assessing VH and its determinants among vaccinators of the HPV campaign. The corresponding WP5 will use results from WP4 to build and test a questionnaire designed to measure VH among health workers involved in the HPV vaccination campaign. Similarly, assessing VH and its determinants among mothers concerned by the HPV vaccination campaign is of crucial interest. The corresponding task (WP6) aims to conceive and test a questionnaire using input from WP1, WP2 and WP3. Last, another main objective of our project is to investigate the role of HPV vaccine controversies in the (social) media and on the internet. As a result, our project aimed at collecting and analyzing data related to HPV vaccine controversies in the Senegalese media and on the internet (WP7), as well as on social media-related data (Tweeter, WP8). Based on a multidisciplinary approach, our project combines qualitative and quantitative methods, and innovative methods to analyze vaccination issues on the social media. From a public health perspective, we expect our project to play a role in contributing to improve population health in Senegal, by identifying barriers to HPV vaccination, among both vaccinators and the general population, and by providing further understanding on beliefs, attitudes and behaviors that could prove useful in the design of information and prevention campaigns, or in the design of training sessions for health workers involved in immunization campaigns (WP9). Another crucial aspect of our project is about building durable partnerships with local academic institutions, and especially the Université Cheikh Anta Diop de Dakar (UCAD) and the Ecole Nationale de la Statistique et de l'Analyse Economique (ENSAE) Dakar.

The scope of this proposal is to contribute to the identification of antivirals against SARS-CoV-2, which unfortunately does not need to be described. Antivirals, because highly potent and safe direct-acting antiviral drugs are available for the treatment of a number of chronic viral infections such as, of course, HIV (~30 approved drugs, used in effective combinations) but also against hepatitis C virus (HCV). Powerful and specifically developed antiviral drugs have been shown to help solve, and potentially cure, virus-induced diseases. This requires integrated approaches involving cheminformatics specialists, HTS experts, biochemists and virologists working on enzyme purification and infected cells, both in pathways and animal models. The Antiviral Drug Design Platform (AD2P) is an IBiSA/ChemBioFrance labeled platform with a long-lasting experience of successful collaborations, both nationally and internationally. Based in Marseille, it gives us the opportunity to work actively together, without being limited by logistical obligations. It should be noted that such an approach has already been performed on the SARS-CoV-1, including screening of many standard chemical libraries. To go further, new chemical libraries should be used to broaden the scope of the chemical space of currently available drugs. We have shown that the CoV-SARS replication complex requires three proteins: nsp7, nsp8 and nsp12. Disruption of this complex with chemical molecules selected to inhibit Protein-Protein Interaction (‘PPI-like inhibitors’) has never been reported. We have such a chemical library available in France, ‘Fr-PPIChem’, thanks to a national consortium financed by the ANR (#ANR-15-CE18-0023 coordinated by X Morelli, partner 3 of the current grant application). The bioassay is based on the inhibition of the activity of the replication complex. Described at the test tube level, we are in the process of scaling up the production/purification of the necessary proteins to develop a non-radioactive test and to miniaturize the test to adapt it to High Thoughput Screening (HTS): our platform will be ready to start screening very soon. It should be noted that this has never been done before for Coronavirus. Screening results will be analyzed, then structural analogs of the hits will be selected in commercially-available libraries and purchased. They will be evaluated in vitro and the best compounds will be tested on infected cells. In the search for analogs, existing drugs will be included. Once iterative work has been carried out, through screening, IC50s determination, biophysical determination and bioinformatics analyses, the most potent molecule(s) will be evaluated in a small animal model that will have been set up in the meanwhile. The expected support of ANR is to: - Set up an HTS assay based on the replication complex of SARS-CoV, a breakthrough - Broaden the chemical space to identify antivirals, a disruptive mean - Set up screening assays on cells infected with potentially different strains of SARS-CoV2, on different cell lines - Set up an animal model to evaluate the potential of selected molecules. In conclusion, we need the support of the ANR to achieve these objectives and conceive unique tools that will be made available to the research community, while at the same time dealing with antivirals, broadening the scope of the chemical space.

Emergence of viral pathogens is a serious public health problem. Some highly pathogenic RNA viruses provoke severe and sometimes fatal human diseases called viral hemorrhagic fevers (VHF). These viruses are of strategic relevance for the French nation. They can potentially emerge in some French territories and affect civilian populations. Furthermore, they are of particular interest for the French army since these pathogens (i) are considered as potential viral bioterrorism agents and (ii) might be present in regions where French troops are deployed. The therapeutics currently used against viruses involved vaccines and antiviral molecules, which have proven to be highly effective in the past. However, the current model of antiviral drug discovery and development is still focused on a given virus, very expensive, and takes a long time to achieve marketing authorization approval. New approaches are therefore needed to address the urgent threats posed by viruses that cause VHF. Indeed, these ‘neglected’ viral pathogens, without clearly identified commercial market cannot take advantage of specific developments at a global scale. This project will therefore aim to unlock these scientific barriers. In order to develop new therapeutics against VHF, the following strategy will be applied: -We will use broad-spectrum antiviral molecules. This strategy will also be potentially advantageous in case of new viral emergence phenomena. -We will use some antiviral molecules already approved in industrialized countries. These drugs will allow for rapid therapeutic proposals to be considered. -Association of two antiviral molecules will be tested. Indeed, a disadvantage of using broad-spectrum molecules is often the need of using high doses to obtain satisfactory antiviral activity. Thus, during this project, a panel of broad-spectrum antiviral molecules with different modes of action will be evaluated on a set of highly pathogenic viruses of the Arenaviridae, Filoviridae and Flaviviridae families and with members of Bunyavirales that cause VHF. Some of these viruses will be manipulated in biosafety level-4 laboratory. The project will take place in three successive stages: -In vitro analysis of each broad-spectrum antiviral compound alone. -In vitro analysis of the best compounds in association two by two in order to find synergetic effects. -In vivo analysis of the best compound associations. A smaller panel of three virus will be use at this stage. The objective of this project is to (i) study systematically in vitro and in vivo activity of broad-spectrum antiviral compounds used alone or in association to find synergetic effects and (ii) to provide at the end one or two associations of broad-spectrum antiviral compounds. In addition, preferably in association with an industrial partner, the development of these therapeutics could subsequently involve a study using non-human primates. This could be the subject of an application for Astrid Maturation funding. Finally, this project will provide a dedicated, structured platform with validated protocols able of characterizing in vitro and in vivo antiviral molecules against highly pathogenic viruses, which could be used in the future by industrial partners or public laboratories.