A lentiviral vector encoding fusion of light invariant chain and mycobacterial antigens induces protective CD4+ T cell immunity

Autor: Jodie Lopez, François Anna, Pierre Authié, Alexandre Pawlik, Min-Wen Ku, Catherine Blanc, Philippe Souque, Fanny Moncoq, Amandine Noirat, David Hardy, Wladimir Sougakoff, Roland Brosch, Françoise Guinet, Pierre Charneau, Laleh Majlessi
Přispěvatelé: Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris] (IP)-TheraVectys-Université Paris Cité (UPCité), Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plate-Forme d’Histopathologie / Histopathology Platform, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Lymphocytes et Immunité - Lymphocytes and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), This project received funding from the European Union's Horizon 2020 research and innovation program (TBVAC2020 643381) and the Marie Sklodowska-Curie grant agreement 665807. The work was also supported by the Programmes Transversaux de Recherche (PTR) 52-17 from the Institut Pasteur and in part by the French National Research Council ANR (ANR-10-LABX-62-IBEID) and the Institut Carnot Pasteur Microbes & Santé. M.-W.K. is a participant of the Pasteur-Paris University (PPU) International PhD Program., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 643381,H2020,H2020-PHC-2014-single-stage,TBVAC2020(2015), Hardy, David, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, TBVAC2020, Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development - TBVAC2020 - - H20202015-01-01 - 2018-12-31 - 643381 - VALID, Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière] (CNR-MyRMA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell Reports
Cell Reports, 2022, 40 (4), pp.111142. ⟨10.1016/j.celrep.2022.111142⟩
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2022.111142⟩
Popis: International audience; Lentiviral vectors (LVs) are highly efficient at inducing CD8+ T cell responses. However, LV-encoded antigens are processed inside the cytosol of antigen-presenting cells, which does not directly communicate with the endosomal major histocompatibility complex class II (MHC-II) presentation pathway. LVs are thus poor at inducing CD4+ T cell response. To overcome this limitation, we devised a strategy whereby LV-encoded antigens are extended at their N-terminal end with the MHC-II-associated light invariant chain (li), which contains an endosome-targeting signal sequence. When evaluated with an LV-encoded polyantigen composed of CD4+ T cell targets from Mycobacterium tuberculosis, intranasal vaccination in mice triggers pulmonary polyfunctional CD4+ and CD8+ T cell responses. Adjuvantation of these LVs extends the mucosal immunity to Th17 and Tc17 responses. A systemic prime and an intranasal boost with one of these LV induces protection against M. tuberculosis. This strategy improves the protective power of LVs against infections and cancers, where CD4+ T cell immunity plays an important role.
Databáze: OpenAIRE