PhD project: Identification of escape H9 and H5 influenza mutants due to vaccination

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INRAE presentation

The French National Research Institute for Agriculture, Food, and Environment (INRAE) is a major player in research and innovation. It is a community of 12,000 people with 272 research, experimental research, and support units located in 18 regional centres throughout France. Internationally, INRAE is among the top research organisations in the agricultural and food sciences, plant and animal sciences, as well as in ecology and environmental science. It is the world’s leading research organisation specialising in agriculture, food and the environment. INRAE’s goal is to be a key player in the transitions necessary to address major global challenges. Faced with a growing world population, climate change, resource scarcity, and declining biodiversity, the Institute has a major role to play in building solutions and supporting the necessary acceleration of agricultural, food and environmental transitions.

Work environment, missions and activities

Background on the VIVACE doctoral Network

While outbreaks of highly pathogenic avian influenza viruses (HPAIV) in Europe used to be rare and geographically contained, the situation has dramatically changed in the last few years with thousands of outbreaks reported in domestic poultry and wild birds. Despite being an intensive field of research, many unknowns remain as we are still struggling to predict HPAIV incursion in poultry, avoid viral spread and limit the socio-economic impact entailed predominantly by control measures. Vaccination of poultry against avian influenza, which used to be prohibited in the European Union (EU) due to trade restrictions, is now being given full consideration, as it is becoming clear that traditional prevention and control approaches alone will not curb the accelerating pace of occurrence of devastating HPAIV epidemics. However, vaccinating poultry does not come without important challenges. The project VIVACE aims at putting together an ambitious doctoral network, composed of 13 PhD scholarships, to contribute to fully integrate poultry vaccination approaches into efficient management strategies for HPAIV. This will be done by unravelling the impact that current and upcoming EU vaccination policies will have on avian influenza virus evolution, surveillance and control strategies, and societal burden of HPAI. For this, VIVACE will use a combination of disciplines from life sciences, epidemiology, computer sciences, and social and behavioural sciences. The consortium gathers 15 leading universities and research institutes and 5 private companies, securing both inter-sectoriality and wide geographic distribution with tailored epidemiological and vaccination contexts.

Objectives of the PhD project

Vaccination will not completely block viral replication and will thus allow viruses to evolve. Immune escape variants are therefore likely to emerge. Interestingly, LPAIV H9N2 have been circulating in Morocco since 2016 and vaccination has quickly been implemented in all types of avian production, including broiler, breeder and layer chickens flocks and turkey farms. Surveillance data show that while Moroccan H9N2 viruses have undergone limited genetic drift in the last 6 years, antigenic drift can be observed, supporting the hypothesis that vaccination pressure may lead to the selection of immune escape variants. In parallel, France has started vaccinating ducks against HPAIV H5 in autumn 2023 and we would like to anticipate emergence of putative escape mutants.The objective of the PhD project are to (i) characterize the genetic and antigenic drifts of field H9N2 AIV in Morocco from 2016 to present time; (ii) predict the emergence of H9 and H5  escape mutants in vitro by combining cell-based and in ovo assays using well characterized chicken sera from the field and limited virus dilutions and then characterize progeny viruses. In parallel we will aim at understanding the amino acids responsible for antigenic drift and compare them with mutations that have already emerged in the field thanks to machine learning approaches. LPAIV H9N2 is used here as a model and extrapolations to the HPAIV H5 situation will be discussed.

Supervisors

Dr. Mariette Ducatez (INRAE, Toulouse, France) is lead scientist at INRAE. Her research activities are conducted in the VIRéMIE group of INRAE/ENVT IHAP unit that she co-leads. She has a strong interest in influenza viruses circulating in avian species and at the animal-human interface, and more specifically in virus evolution. She co-authored more than 130 peer-reviewed research articles and supervised multiple graduate students. She is one of the three co-coordinators of the VIVACE project.

Prof. Siham Fellahi is the Head of the Avian Pathology Unit at IAV Hassan II in Rabat, Morocco. She has a strong interest in poultry health, the development of new protection strategies and diagnostic tools into avian diseases including avian influenza, avian infectious bronchitis, infectious bursal disease and Newcastle disease, etc. She contributed to around 80 publications, including papers in international referee’s journals, papers and abstracts published in the proceeding of conferences.

 

Key references

1. Arbani O., Ducatez M.F., Kadja-Wonou M., Salamat F., Kichou F., EL Houadfi M., Fellahi S., Development of an experimental model using cold stress to assess the pathogenicity of two Moroccan AI H9N2 isolates from 2016 and 2022 in commercial broiler chickens. PloS One. 2025, 20(4):e0320666, doi: 10.1371/journal.pone.0320666.
2. European Food Safety Authority, European Centre for Disease Prevention and Control, European Union Reference Laboratory for Avian Influenza, Alexakis L., Buczkowski H., Ducatez M., Fusaro A., Gonzales J.L., Kuiken T., Ståhl K., Staubach C., Svartström O., Terregino C., Willgert K., Melo M., Kohnle L., Avian influenza overview December 2024-March 2025. EFSA Journal. 2025, doi: 10.2903/j.efsa.2025.9352.
3. Sanogo I.N., Guinat C., Dellicour S., Diakité M.A., Niang M., Koita O.A., Camus C., Ducatez M., Genetic insights of H9N2 avian influenza viruses circulating in Mali and phylogeographic patterns in Northern and Western Africa. Virus Evolution. 2024, 10(1):veae011. doi: 10.1093/ve/veae011.
4. Sanogo I.N., Djegui F., Akpo Y., Gnanvi C., Dupré G., Rubrum A., Jeevan T., McKenzie P., Webby R.J., Ducatez M.F., Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus in Poultry, Benin, 2021. Emerging Infectious Diseases. 2022; 8(12):2534-2537. doi: 10.3201/eid2812.221020.
5. Fusade-Boyer M., Djegui F., Batawui K., Byuragaba D.K., Jones J.C., Wabwire-Mangeni F., Erima B., Atim G., Ukuli Q.A., Tugume T., Dogno K., Adjabli K., Nzuzi M., Adjin R., Jeevan T., Rubrum A., Go-Maro W., Kayali G., McKenzie P., Webby R.J., Ducatez M.F., Antigenic and molecular characterization of low pathogenic avian influenza A(H9N2) viruses in sub-Saharan Africa from 2017 through 2019. Emerging Microbes and Infections. 10(1):753-761. 2021. doi: 10.1080/22221751.2021.1908097.
6. El Houadfi M., Fellahi S., Nassik S., Guérin J.L., Ducatez M.F. First outbreaks and phylogenetic analyses of avian influenza H9N2 viruses isolated from poultry flocks in Morocco. Virology Journal. 13(1), 2016,140. doi:10.1186/s12985-016-0596-1.

Research location

The PhD candidate will conduct his/her research at the French National Research Institute for Agriculture, Food, and Environment (INRAE), within the Host-Pathogen Interaction Unit (IHAP) on the campus of the National Veterinary School of Toulouse (ENVT), France. The candidate will be involved in extensive laboratory work in France and have secondment periods at the Institut Agronomique et Vétérinaire Hassan II in Rabat (Morocco, with Siham Fellahi), to access field surveillance of H9N2 viruses and be trained in machine learning; and at the Erasmus University Medical Center in Rotterdam (the Netherlands, with Mathilde Richard) to perform antigenic cartography of both field and experimentally generated H9N2 viruses. 

Training and skills

The ideal PhD candidate should possess a Master’s degree or equivalent in Virology, Infectiology, Microbiology, Veterinary Medicine, Biology, or a related field, with a solid academic foundation in infectious diseases, molecular and cellular biology. Candidates should have prior research experience in laboratory or field studies, particularly in virology, microbiology, or animal health, and demonstrate proficiency in molecular diagnostic techniques such as RT-qPCR and pathogen detection. Familiarity with cellular biology techniques is essential, skills in bioinformatics would be advantageous. The candidate should exhibit strong scientific writing and communication skills, with fluency in English; knowledge of French would be a bonus but not mandatory at all. Strong organizational and time-management skills, the ability to work independently and collaboratively within multidisciplinary teams, and a willingness to work in biocontainment facilities are crucial. As the project is part of the VIVACE doctoral network (Marie Skłodowska-Curie Action), candidates must meet mobility requirements by not having resided or conducted their main activities (work, studies, etc.) in France for more than twelve months during the three years preceding the start of the PhD project.

INRAE's life quality

By joining our teams, you benefit from (depending on the type of contract and its duration):

- up to 30 days of annual leave + 15 days "Reduction of Working Time" (for a full time);
- parenting support: CESU childcare, leisure services;
- skills development systems: training, career advise;
- social support: advice and listening, social assistance and loans;
- holiday and leisure services: holiday vouchers, accommodation at preferential rates;
- sports and cultural activities;
- collective catering.

How to apply

Please send your application before 31 May 2025 to Dr. Mariette Ducatez (mariette.ducatez@envt.fr), and Dr. Siham Fellahi (s.fellahi@iav.ac.ma).

Your application should include:

• your CV
• two reference letters
• a short motivation letter (max 1 page) where you state why you are interested and what experience you have to address the aspects of the project

Online interviews of shortlisted candidates will be held in June 2025.

For further information, please contact Dr. Mariette Ducatez (mariette.ducatez@envt.fr), or Dr. Siham Fellahi (s.fellahi@iav.ac.ma).