IMRB - Mondor Biomedical Research InstituteGodot

ACCELERation of the development of innovATive vaccinES against HIV/AIDS and (re)-emerging infectious diseases (ACCELERATES)

Contacts

Head Véronique Godot

Tél.: 01 49 81 39 12
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Team description

The team comprises approximately 50 members, including PhD scientists, physician-scientists (MD, PhD), associate and full professors, clinicians, engineers, and trainees. It provides a highly productive environment at the interface between biomedical research, the Department of Infectious and Tropical Diseases and Clinical Immunology at Henri Mondor Hospital, and Université Paris-Est Créteil (UPEC).

The team is affiliated with the Vaccine Research Institute (VRI), a Laboratory of Excellence (LabEx) established in 2011 during the first wave of the French Programme d’Investissements d’Avenir (PIA1) and directed by Professor Yves LÉVY (https://vaccine-research-institute.fr/fr/). It is also part of the IHU Sepsis, led by Professor Djillali ANNANE (https://ihu-sepsis.fr/).

The team brings together complementary expertise in immune monitoring of patients and clinical-trial participants (Aurélie WIEDEMANN and Christine LACABARATZ); epitope mapping (Mathieu SURENAUD and Sylvain CARDINAUD); dendritic-cell-targeted vaccine development (Sylvain CARDINAUD, Sandy ZURAWSKY, and Gérard ZURAWSKY); proteomics (Mathieu SURENAUD); genomics (Cécile LEFEBVRE); cancer immunotherapy and associated mouse models (Sylvain MEUNIER, Assistant Professor); immunogenetics of infectious diseases (Zineb SBIHI, Junior Professor); cell and gene therapy (Anne GALY, Head of ART-TG); preclinical models and tissue imaging (Véronique GODOT). These activities are supported by close interaction with the local clinical department, headed by Jean-Daniel LELIÈVRE, and by strong collaborations with clinical departments throughout France.

The team develops integrated translational research programmes to design and evaluate innovative vaccines against emerging and re-emerging infectious diseases. Its research also focuses on vaccine-based and combinatorial immunotherapeutic strategies, including cell and gene therapies for HIV/AIDS and virus-associated cancers.

Research program

Aim 1. Mechanisms of CD40-targeting vaccines

We investigate the mechanisms underlying the magnitude, breadth and durability of immune responses elicited by CD40-targeting vaccines. Using SARS-CoV-2 or HIV-1 as a model, we compare CD40-targeting, mRNA, nanoparticle, and MVA vaccine platforms that deliver related antigens, with particular emphasis on long-term antibody responses, memory B cells, and CD8⁺ T memory stem cells (Tscm).

Aim 2. CD40 platform in new settings

We expand the CD40-targeting platform to populations and diseases for which current vaccination strategies remain insufficient. The team investigates the immunogenicity, durability and protective efficacy of CD40.SARS-CoV-2 vaccines in ageing and immunocompromised mouse models, including the evaluation of innovative adjuvants and immune modulators. In parallel, we develop therapeutic CD40-targeting vaccines against tuberculosis; advance therapeutic vaccines for HPV-associated cancers; and explore APC-targeting approaches against antibiotic-resistant bacterial infections. These programmes aim to optimise vaccine formulations, delivery routes, antigen selection and combination strategies.

Aim 3. New APC targets and immunogens

We develop next-generation antigen-presenting-cell-targeting vaccination strategies to improve antibody quality and durability. We investigate Langerhans-cell targeting through the langerin receptor to promote T follicular helper-cell and germinal-centre responses, particularly for the induction and maturation of HIV-1-neutralising antibodies. This programme evaluates native-like and multimeric HIV-1 Env immunogens, including SOSIP-like trimers and germline-targeting constructs, and extends this approach to CD40 targeting and additional pathogens such as Ebola virus, Nipah virus and Bordetella pertussis. We explore improved formulations and non-invasive topical or patch-based delivery strategies for APC-targeting vaccines.

Aim 4. Gene-based immunotherapies

We establish gene-based immunotherapies for chronic infectious diseases, with a major focus on HIV-1, by developing engineered human B cells that express broadly neutralising anti-HIV-1 antibodies, using genome-editing technologies and complementary mRNA/lipid nanoparticle approaches. This programme aims to create durable, controllable and potentially curative immunotherapeutic strategies for people living with HIV-1.

Aim 5. Clinical immunomonitoring and translational studies

We conduct comprehensive immunomonitoring of patients with infectious diseases and of participants enrolled in national and international vaccine clinical trials by characterising innate, T-cell, and B-cell responses to infection and vaccination, with the aim of identifying immune correlates of protection, vaccine-response biomarkers, and disease endotypes. These activities encompass SARS-CoV-2 infection and long COVID, bacterial and viral sepsis, vaccination in immunocompromised individuals, and clinical evaluation of vaccine candidates against HIV-1, Ebola virus, HPV-associated cancers and COVID-19.

Keywords:

APC-targeting vaccines – CD40 vaccine platform – Durable immune memory – HIV-1 broadly neutralising antibodies – Gene-based immunotherapies

Selected publications

Levy Y*, Lelievre JD *, L Assoumou, , E Aznar, F Pulido, G Tambussi, M Crespo, A Meybeck, , J-M Molina, C Delaugerre, J Izopet, , G Peytavin, F Cardon, A Diallo, R Lancar, L Béniguel, D Costagliola, Addition of maraviroc versus placebo to standard antiretroviral therapy for initial treatment of advanced HIV-infection : a double-blind randomized controlled trial

Annals of Internal Medicine, 11 february 2020

Aurélie Wiedemann , Emile Foucat, , Hakim Hocini, Cécile Lefebvre, Mélany Durand Miriam Kruger, Alpha Kabinet Keita, Ahidjo Ayouba, , Stéphane Mély, , José-Carlos Fernandez, , Abdoulaye Touré, , Slim Fourati, M.D., Claire Lévy-Marchal, Hervé Raoul, Eric Delaporte , Lamine Koivogui , Rodolphe Thiébaut , Christine Lacabaratz*, and Yves Lévy* for the PostEboGui Study Group Long-lasting severe immune dysfunction in Ebola virus disease survivors.

Nature Communications, 2020 , Jul 24, vol 11, 1-11

Surenaud M, Montes M, Lindestam Arlehamn CS, Sette A, Banchereau J, Palucka K, Lelièvre JD, Lacabaratz C, Lévy Y. “Anti-HIV potency of T-cell responses elicited by dendritic cell therapeutic vaccination.”

PLoS Pathog. 2019 Sep 9;15(9):e1008011. doi: 10.1371/journal.ppat.1008011

Thiébaut R, Hejblum BP, Hocini H, Bonnabau H, Skinner J, Montes M, Lacabaratz C, Richert L, Palucka K, Banchereau J, Lévy Y. Gene Expression Signatures Associated With Immune and Virological Responses to Therapeutic Vaccination With Dendritic Cells in HIV-Infected Individuals

Front Immunol. 2019 Apr 24;10:874. doi: 10.3389/fimmu.2019.00874. eCollection 2019

Lylia Hani, Antoine Chaillon, Marie-Laure Nere, Nicolas Ruffin, Joudy Alameddine, Maud Salmona, José-Luiz Lopez Zaragoza, Davey M. Smith, Olivier Schwartz, Jean-Daniel Lelièvre, Constance Delaugerre, Yves Lévy and Nabila Seddiki “Proliferative memory SAMHD1low CD4+ T cells harbour high levels of HIV-1 DNA with compartmentalized viral populations”

PLoS Pathog. 2019 Jun 20;15(6):e1007868. doi: 10.1371/journal.ppat.1007868. eCollection 2019 Jun.

Hakim Hocini, Henri Bonnabau, Christine Lacabaratz, Cécile Lefebvre, Pascaline Tisserand, Emile Foucat, Jean-Daniel Lelièvre, Olivier Lambotte, Asier Sáez-Cirión, Pierre Versmisse, Rodolphe Thiébaut, and Yves Lévy "HIV controllers have low inflammation associated with a strong HIV-specific immune response in blood"

J Virol. 2019 Feb 27. pii: JVI.01690-18. doi: 10.1128/JVI.01690-18

Flamar AL, Bonnabau H, Zurawski S, Lacabaratz C, Montes M, Richert L, Wiedemann A, Galmin L, Weiss D, Cristillo A, Hudacik L, Salazar A, Peltekian C, Thiebaut R, Zurawski G, Levy Y. HIV-1 T cell epitopes targeted to Rhesus macaque CD40 and DCIR: A comparative study of prototype dendritic cell targeting therapeutic vaccine candidates.

PLoS One. 2018 Nov 30;13(11):e0207794. doi: 10.1371/journal.pone.0207794. eCollection 2018

Cheng L, Wang Q, Li G, Banga R, Ma J, Yu H, Yasui F, Zhang Z, Pantaleo G, Perreau M, Zurawski S, Zurawski G, Levy Y, Su L TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs

J Clin Invest. 2018 Oct 1;128(10):4387-4396. doi: 10.1172/JCI99005

Palich R, Ghosn J, Chaillon A, Boilet V, Nere ML, Chaix ML, Delobel P, Molina JM, Lutch F, Bouchaud O, Rieux V, Thiebaut R, Levy Y, Delaugerre C, Lelievre JD; « Viral rebound in semen after antiretroviral treatment interruption in an HIV therapeutic vaccine double-blind trial ».

AIDS. 2018 Oct 15. doi: 10.1097/QAD.0000000000002058.

Planchais C, Hocqueloux L, Ibanez C, Gallien S, Copie C, Surenaud M, Kök A, Lorin V, Fusaro M, Delfau-Larue MH, Lefrou L, Prazuck T, Lévy M, Seddiki N, Lelièvre JD, Mouquet H, Lévy Y, Hüe S. « Early Antiretroviral Therapy Preserves Functional Follicular Helper T and HIV-Specific B Cells in the Gut Mucosa of HIV-1-Infected Individuals.»

J Immunol. 2018 Apr 9. pii: ji1701615. doi: 10.4049/jimmunol.1701615.

ACCELERation of the development of innovATive vaccinES against HIV/AIDS and (re)-emerging infectious diseases (ACCELERATES)

Contacts

Research program

Keywords:

Selected publications

The team

Actualités de l'équipe