Research project
It is now admitted that neutralizing antibodies play a central role in HIV protection. Such antibodies are therefore the gold standard to induce by vaccination. However, such antibodies are rare and extremely difficult to induce. The project of C. Moog and coworkers is to characterize the functional inhibitory activities of such antibodies in order to improve their induction by vaccination. The Moog group demonstrated that the use of primary HIV isolates are more relevant as the one of adapted strains to detect protective antibodies. They were pioneers in identifying the role of Fc-mediated antibody inhibitory functions in protection against HIV to uncover novel strategies for prevention and treatment of HIV infection and virus-associated diseases. C. Moog and her coworkers identified antibodies displaying various HIV inhibitory functions (phagocytosis, antibody dependent cellular cytotoxicity, virus capture etc) without any neutralizing activity. Their current research project is focused on understanding the inhibitory role of Abs during the early stage of HIV transmission at the mucosal site i.e. to characterize Ab-mediated inhibition in antigen presenting cells and on ex-vivo tissue explants, inhibition of HIV cell-to-cell transmission and lysis of infected cells (ADCC), as well as the mechanisms of Fc-Fc receptor mediated inhibition at mucosa sites. Moreover, in collaboration with R. Carapito, they determine the Fc receptor genotype in various HIV patient cohorts to define the role of this host factor on HIV evolution. These research projects will open a new area of investigations for the induction of functional inhibitory antibodies by vaccination.
COLLABORATIONS
The group has established multiple collaborations with national and international scientists as Y. Levy, (Creteil, France), O. Lambotte (Kremlin-Bicêtre, France), R. Le Grand (CEA, France), B. Autran (Pitié-Salpêtrière, France), R. Shattock (Imperial College London, UK), C. Geldmacher (LMU Munich, Germany), E. Karamov (Moscow, Russia), S. Zolla-Pazner (Mount Sinai, NY, USA), D. Montefiori (Duke, USA).
They are part of National (LabEx VRI), European (Horizon 2020, EHVA project) and International (ADCC working group, HIP/HVTN) networks aiming to develop new vaccine strategies and promoting HIV vaccine trials for search of correlates of protection.
FUNDING
- ANRS
- SIDACTION
- LabEx
- 5th, 6th, and 7th PCRD
- Horizon 2020
- EU-Russia research and innovation cooperation
- NIH
PUBLICATIONS
Lewis GK, Ackerman ME, Scarlatti G, Moog C, Robert-Guroff M, Kent SJ, Overbaugh J, Reeves RK, Ferrari G, Thyagarajan B. Knowns and Unknowns of Assaying Antibody-Dependent Cell-Mediated Cytotoxicity Against HIV-1. Front Immunol. 2019 May 10;10:1025. doi: 10.3389/fimmu.2019.01025. eCollection 2019.
Ducloy C, Bin Su, Luzia Mayr, Jéromine Klingler, Thomas Decoville, SylvieSchmidt, Géraldine Laumond, Nathalie Salomé, Seiamak Bahram and Christiane Moog HIV transmission from infected CD4R T cells to allogenic T and dendritic cells is inhibited by broadly neutralizing antibodies. 2018, AIDS, 32, 1240-45.
HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection. Rouers A, Klingler J, Su B, Samri A, Laumond G, Even S, Avettand-Fenoel V, Richetta C, Paul N, Boufassa F, Hocqueloux L, Mouquet H, Rouzioux C, Lambotte O, Autran B, Graff-Dubois S, Moog C, Moris A EBioMedicine, 2017
Non-neutralizing Antibodies Targeting the V1V2 Domain of HIV Exhibit Strong Antibody-Dependent Cell-mediated Cytotoxic Activity. Mayr L, Decoville T, Schmidt S, Laumond G, Klingler J, Ducloy C, Bahram S, Zolla-Pazner S, Moog C. Sci Rep, 2017
Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. Santra S, Tomaras GD, Warrier R, Nicely NI, Liao HX, Pollara J, Liu P, Alam SM, Zhang R, Cocklin SL, Shen X, Duffy R, Xia SM, Schutte RJ, Pemble Iv CW, Dennison SM, Li H, Chao A, Vidnovic K, Evans A, Klein K, Kumar A, Robinson J, Landucci G, Forthal DN, Montefiori DC, Kaewkungwal J, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Robb ML, Michael NL, Kim JH, Soderberg KA, Giorgi EE, Blair L, Korber BT, Moog C, Shattock RJ, Letvin NL, Schmitz JE, Moody MA, Gao F, Ferrari G, Shaw GM, Haynes BF. PLoS Pathog, 2015
Short Communication: Exploring Antibody Potential as Prophylactic/Therapeutic Strategies for Prevention of Early Mucosal HIV-1 Infection. Su B, Peressin M, Ducloy C, Penichon J, Mayr LM, Laumond G, Schmidt S, Decoville T, Moog C.AIDS Res Hum Retroviruses, 2015
Single-chain protein mimetics of the N-terminal heptad-repeat region of gp41 with potential as anti-HIV-1 drugs. Crespillo S, Camara-Artigas A, Casares S, Morel B, Cobos ES, Mateo PL, Mouz N, Martin CE, Roger MG, El Habib R, Su B, Moog C, Conejero-Lara F. Proc Natl Acad Sci USA, 2014
Antibodies Inhibit HIV-1 Infection of Plasmacytoid Dendritic Cells by an FcγRIIa Independent Mechanism and Do Not Diminish Cytokines Production. Lederle A, Su B, Holl V, Penichon J., Schmidt S., Decoville T., Laumond G., Moog C. Scientific Report, 2014
Dendritic cell-lymphocyte cross talk downregulates host restriction factor SAMHD1 and stimulates HIV-1 replication in dendritic cells. Su B, Biedma ME, Lederle A, Peressin M, Lambotin M, Proust A, Decoville T, Schmidt S, Laumond G, Moog C. Virol, 2014
Broadly Neutralizing Antibody VRC01 Prevents HIV-1 Transmission from Plasmacytoid Dendritic Cells to CD4 T Lymphocytes. Su B, Lederle A, Laumond G, Ducloy C, Schmidt S, Decoville T, Moog C. J Virol, 2014
Efficient transfer of HIV-1 in trans and in cis from Langerhans dendritic cells and macrophages to autologous T lymphocytes. Peressin M, Proust A, Schmidt S, Su B, Lambotin M, Biedma ME, Laumond G, Decoville T, Holl V, Moog C. AIDS, 2014
Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal SHIV challenge in macaques. Moog C, Dereuddre-Bosquet N, Teillaud JL, Biedma ME, Holl V, VanHam G, Heyndrickx L, Van Dorsselaer A, Katinger D, Vcelar B, Zolla-Pazner S, Mangeot I, Kelly C, Shattock R, Le Grand R. Mucosal Immunol, 2014