Fiche de description de la thèse
Délégation Régionale Paris 12
Unité de recherche n° : U955 Directeur : Jorge BOCZKOWSKI
Équipe : Vaccine Research Institute (Eq16) Responsable : Prof. Yves Levy
Lieu d’activité :
Institut Mondor de Recherche Biologique
Hôpital Henri Mondor, Bat. Recherche R1
51 avenue du Maréchal de Lattre de Tassigny
94010 CRETEIL Cedex
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Intitulé du poste : HIV immune responses promoted by a vaccine targeting epidermal Langerhans cell : in situ study of the mechanisms of induction of Tfh and Germinal center B cells.
Durée du recrutement souhaitée : 36 mois
Supervisor: Sylvain CARDINAUD, PhD
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Corps de recrutement :
x Doctorant o Post-doctorant o Chercheur o Ingénieur d’études o Ingénieur de recherche
oAssistant-ingénieur o Technicien de la recherche o Adjoint technique o
Branche d’activité professionnelle (BAP)* Biologie et santé, Sciences de la vie et de la terre
Emploi type *: Ingénieur-e en techniques biologiques
* Listes des BAP et emplois-types sont consultables via le site internet http://www.enseignementsuprecherche.gouv.fr/cid106062/referens-le-referentiel-2016-des-emplois-types-de-la-recherche-et-de-lenseignement-superieur.html
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Missions du poste :
Background: The main goal for the development of an HIV-1 vaccine remains the induction of protective
antibodies. New modes of antigen delivery are warranted to improve the quality of immune responses. Our
proposal is to target HIV antigen to receptors expressed on dendritic cells (DC) via fused monoclonal Ab
(mAb) to promote cellular and humoral responses. We previously showed that targeting of the skin
Langerhans cells (LC) with anti-Langerin mAb fused to HIV-1 Envelop (LC.Env) drives antigen-specific
humoral responses, either in mice or using in vitro cultures of human LCs (Kervevan J. PLoS Path 2021).
Hypothesis and Objectives: The PhD candidate will i) decipher in vivo the molecular and cellular
mechanisms involved in the induction of B cell responses by the LC.Env vaccination using preclinical
models, ii) characterize in detail the humoral response, following the magnitude and the quality of
circulating Env-specific IgG and untangling the maturation of the B cells, iii) target to LC other innovative
HIV vaccine antigens developed in house or by our collaborators, and study whether they improve in situ
the humoral responses.
Significance: Clinical development of DC-targeting vaccines might bring innovation in the delivery of
antigen and a new way to elicit broad and potent integrated immune responses. Recent clinical results of
aCD40.Env DC-targeting vaccine combined with TLR3 adjuvant are promising. Next generation of aLC
vaccine would help to improve responses to conformational trimer Env immunogen with the aim to elicit
NeutAb.
PROFIL DE POSTE
Activités principales :
• Production of innovative DC-targeting vaccines and in vivo immunological approaches.
• Analysis of bibliography, step-by-step reports of activity, redaction of peer-reviewed articles
• Oral communications and poster presentation in international congress (immunology, vaccinology)
Compétences requises :
• Solid knowledges in antiviral immunology and/or vaccinology
• Practical experience for culturing cells in vitro, and assessing immunological responses (ELISpot,
FACS, Luminex)
• Experience in manipulating animals and validated training for ethics are a plus.
• Good level in English
Environnement et contexte de travail :
The VRI is a network of national and international clinical and research teams sharing the goal to develop
innovative therapeutic and prophylactic vaccines and tools to analyze biological responses to
immunotherapies and vaccines against HIV (and emerging infectious diseases). The overarching goal is
the generation of novel DC-based preventive and therapeutic vaccine candidates inducing potent
neutralizing and non-neutralizing Ab responses and T cell responses. The VRI-U955 laboratory includes
BSL-2/3 and animal facilities endowed with last generation equipment (e.g., flow cytometers, cell sorter,
Luminex and Illumina sequencing technology on HiSeq system) required for the successful implementation
of the PhD program.
Contraintes spécifiques :
Compliance with regulations on working hours and leave entitlements. The candidate must comply with the
health and safety obligations submitted to the laboratory.
Diplôme requis :
Master 2 in the field of molecular and cell biology, immunology, vaccinology
Formation et expérience professionnelle souhaitées :
Internship(s) carried out in an academic research laboratory (biochemistry and/or immunology).
Remarques diverses :
Application (with CV) should be addressed to
– Dr Sylvain CARDINAUD (sylvain.cardinaud@inserm.fr)
– Prof. Véronique GODOT (veronique.godot@inserm.fr)
– Prof. Yves LEVY (yves.levy@inserm.fr)