Phd Project: Identification of Escape H9 and H5 Influenza Mutants Due to Vaccination

**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**

**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.

**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.

**Key references**

1. Arbani O.,, 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/jou