PhD grants "Integrative screening of Staphylococcus aureus candidate antigens for vaccine developments" (SSBCV)

• 36 months doctoral funding (October 2021 to September 2024)
• Keywords

Cell-mediated immunity, Immunopeptidomics, Bioinformatics, Vaccines, Bovine mastitis

• Profile and skills required

Applicants should have a broad unterstanding of cell biology and immunology. She/he will work in collaboration with the staff of IBIR and other research teams located at INRAE Centre Val de Loire. She/he should be interested in working in a multidisciplinary and multicultural environment and should have good knowledge of English. A keen interest in in silico approaches applied to immunology will be appreciated.

Scientific skills:

- Good background in cell biology techniques. Experience in blood cells primary culture will be appreciated;

- Knowledge of the principles of multicolor flow cytometry analysis and protocols design. Practical experience with softwares for flow cytometry data acquisition and analysis (DIVA, FlowJo, Kaluza);

- Good scientific writing skills;

- Knowledge of scientific English.

Required qualities:

- Scientifique rigor;

- Good capacity to communicate and open-minded attitude.

• Project description

Limiting the overall use of antibiotics constitutes a topical challenge for the breeding industry. To reach this objective, vaccination plays a critical role by reducing the incidence and severity of high-impact diseases. New alternatives to conventional antibody-based vaccines are necessary for controlling numerous animal diseases, including intramammary infections by Staphylococcus aureus in dairy cattle. Because the selection of relevant antigens is a critical step of vaccine production pipelines, this project proposes an innovative and multidisciplinnary approach to identify S. aureus antigens able to induce cell-mediated immunity in bovine. Our preliminary observations indicate variable individual responses against S. aureus in affected herds and this variation could be associated to the presentation of distinct antigens in the context of protective or tolerogenic responses. To address this issue, we will combine an analysis of host response to S. aureus with an antigenic peptide screening based on state-of-the-art immunopeptidomics and bioinformatics, in order to identify the antigens associated with protection or tolerance. The capacity of our strategy to distinguish these antigens will be further evaluated by their expression in a home-made yeast-based vector and validation using an in vitro immunostimulation test. This application is part of a project financed by the ANR (CelBoVax) focused on the development of candidate vaccines for bovine staphylococcal mastitis.

• References

1. Rainard, P., et al., Knowledge gaps and research priorities in Staphylococcus aureus mastitis control. Transbound Emerg Dis, 2018. 65 Suppl 1: p. 149-165

2. Rappuoli, R., Reverse vaccinology, a genome-based approach to vaccine development. Vaccine, 2001. 19(17-19): p. 2688-91

3. Purcell, A.W., S.H. Ramarathinam, and N. Ternette, Mass spectrometry-based identification of MHC-bound peptides for immunopeptidomics. Nat Protoc, 2019. 14(6): p. 1687-1707

4. Farrell, D., et al., Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis. Microb Genom, 2016. 2(8): p. e000071

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