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1. A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Author

Changeux, Jean-Pierre, Amoura, Zahir, Rey, Felix A., and Miyara, Makoto

Subjects
Covid-19, smoking, nicotinic receptors, clinical trials of nicotine patches, Biology (General), QH301-705.5
Abstract

SARS-CoV-2 epidemics raises a considerable issue of public health at the planetary scale. There is a pressing urgency to find treatments based upon currently available scientific knowledge. Therefore, we tentatively propose a hypothesis which hopefully might ultimately help save lives. Based on the current scientific literature and on new epidemiological data which reveal that current smoking status appears to be a protective factor against the infection by SARS-CoV-2 [1], we hypothesize that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection.

Published
2020
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3. TMPRSS2 is a functional receptor for human coronavirus HKU1

Author

Saunders, Nell, Fernandez, Ignacio, Planchais, Cyril, Michel, Vincent, Rajah, Maaran Michael, Baquero Salazar, Eduard, Postal, Jeanne, Porrot, Francoise, Guivel-Benhassine, Florence, Blanc, Catherine, Chauveau-Le Friec, Gaëlle, Martin, Augustin, Grzelak, Ludivine, Oktavia, Rischa Maya, Meola, Annalisa, Ahouzi, Olivia, Hoover-Watson, Hunter, Prot, Matthieu, Delaune, Deborah, Cornelissen, Marion, Deijs, Martin, Meriaux, Véronique, Mouquet, Hugo, Simon-Lorière, Etienne, van der Hoek, Lia, Lafaye, Pierre, Rey, Felix, Buchrieser, Julian, and Schwartz, Olivier

Published
2023
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5. Broad sarbecovirus neutralization by combined memory B cell antibodies to ancestral SARS-CoV-2

Author

Planchais, Cyril, Fernández, Ignacio, Chalopin, Benjamin, Bruel, Timothée, Rosenbaum, Pierre, Beretta, Maxime, Dimitrov, Jordan D., Conquet, Laurine, Donati, Flora, Prot, Matthieu, Porrot, Françoise, Planas, Delphine, Staropoli, Isabelle, Guivel-Benhassine, Florence, Baquero, Eduard, van der Werf, Sylvie, Haouz, Ahmed, Simon-Lorière, Etienne, Montagutelli, Xavier, Maillère, Bernard, Rey, Félix A., Guardado-Calvo, Pablo, Nozach, Hervé, Schwartz, Olivier, and Mouquet, Hugo

Published
2024
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6. Novel requirements for HAP2/GCS1-mediated gamete fusion in Tetrahymena

Author

Pinello, Jennifer F., Loidl, Josef, Seltzer, Ethan S., Cassidy-Hanley, Donna, Kolbin, Daniel, Abdelatif, Anhar, Rey, Félix A., An, Rocky, Newberger, Nicole J., Bisharyan, Yelena, Papoyan, Hayk, Byun, Haewon, Aguilar, Hector C., Lai, Alex L., Freed, Jack H., Maugel, Timothy, Cole, Eric S., and Clark, Theodore G.

Published
2024
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7. A synthetic delivery vector for mucosal vaccination

Author

Billet, Anne, Hadjerci, Justine, Tran, Thi, Kessler, Pascal, Ulmer, Jonathan, Mourier, Gilles, Ghazarian, Marine, Gonzalez, Anthony, Thai, Robert, Urquia, Pauline, Van Baelen, Anne-Cécile, Meola, Annalisa, Fernandez, Ignacio, Deville-Foillard, Stéphanie, MacDonald, Ewan, Paolini, Léa, Schmidt, Frédéric, Rey, Félix A., Kay, Michael S., Tartour, Eric, Servent, Denis, and Johannes, Ludger

Published
2023
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8. SARS-CoV-2 Omicron BA.1 breakthrough infection drives late remodeling of the memory B cell repertoire in vaccinated individuals

Author

Sokal, Aurélien, Barba-Spaeth, Giovanna, Hunault, Lise, Fernández, Ignacio, Broketa, Matteo, Meola, Annalisa, Fourati, Slim, Azzaoui, Imane, Vandenberghe, Alexis, Lagouge-Roussey, Pauline, Broutin, Manon, Roeser, Anais, Bouvier-Alias, Magali, Crickx, Etienne, Languille, Laetitia, Fournier, Morgane, Michel, Marc, Godeau, Bertrand, Gallien, Sébastien, Melica, Giovanna, Nguyen, Yann, Canoui-Poitrine, Florence, Pirenne, France, Megret, Jérôme, Pawlotsky, Jean-Michel, Fillatreau, Simon, Reynaud, Claude-Agnès, Weill, Jean-Claude, Rey, Félix A., Bruhns, Pierre, Mahévas, Matthieu, and Chappert, Pascal

Published
2023
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9. Novel Toscana Virus Reverse Genetics System Establishes NSs as an Antagonist of Type I Interferon Responses.

Author

Woelfl, Franziska, Léger, Psylvia, Oreshkova, Nadia, Pahmeier, Felix, Windhaber, Stefan, Koch, Jana, Stanifer, Megan, Roman Sosa, Gleyder, Uckeley, Zina M, Rey, Felix A, Boulant, Steeve, Kortekaas, Jeroen, Wichgers Schreur, Paul J, and Lozach, Pierre-Yves

Subjects
Kidney, Cell Line, Vero Cells, Animals, Humans, Sandfly fever Naples virus, DNA-Directed RNA Polymerases, Interferon-beta, Viral Proteins, Viral Nonstructural Proteins, Antibodies, Viral, Mutation, Genome, Viral, Cricetinae, Reverse Genetics, A549 Cells, Insecta, Chlorocebus aethiops, Arbovirus, Bunyavirales, Phenuiviridae, Phlebovirus, Toscana virus, interferon, neglected diseases, reverse genetics, sand fly fever, Genetics, Immunization, Biotechnology, Vaccine Related, Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Microbiology
Abstract

The sand fly-borne Toscana virus (TOSV) is the major cause of human meningoencephalitis in the Mediterranean basin during the summer season. In this work, we have developed a T7 RNA polymerase-driven reverse genetics system to recover infectious particles of a lineage B strain of TOSV. The viral protein pattern and growth properties of the rescued virus (rTOSV) were found to be similar to those of the corresponding wild-type (wt) virus. Using this system, we genetically engineered a TOSV mutant lacking expression of the non-structural protein NSs (rTOSVɸNSs). Unlike rTOSV and the wt virus, rTOSVɸNSs was unable to (i) suppress interferon (IFN)-b messenger RNA induction; and (ii) grow efficiently in cells producing IFN-b. Together, our results highlight the importance of NSs for TOSV in evading the IFN response and provide a comprehensive toolbox to investigate the TOSV life cycle in mammalian and insect host cells, including several novel polyclonal antibodies.

Published
2020

11. SARS‐CoV‐2‐related bat virus behavior in human‐relevant models sheds light on the origin of COVID‐19

Author

Temmam, Sarah, Montagutelli, Xavier, Herate, Cécile, Donati, Flora, Regnault, Béatrice, Attia, Mikael, Baquero Salazar, Eduard, Chretien, Delphine, Conquet, Laurine, Jouvion, Grégory, Pipoli Da Fonseca, Juliana, Cokelaer, Thomas, Amara, Faustine, Relouzat, Francis, Naninck, Thibaut, Lemaitre, Julien, Derreudre‐Bosquet, Nathalie, Pascal, Quentin, Bonomi, Massimiliano, Bigot, Thomas, Munier, Sandie, Rey, Felix A, Le Grand, Roger, van der Werf, Sylvie, and Eloit, Marc

Published
2023
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12. Decentralized Resource Allocation via Dual Consensus ADMM

Author

Banjac, Goran, Rey, Felix, Goulart, Paul, and Lygeros, John

Subjects
Mathematics - Optimization and Control
Abstract

We consider a resource allocation problem over an undirected network of agents, where edges of the network define communication links. The goal is to minimize the sum of agent-specific convex objective functions, while the agents' decisions are coupled via a convex conic constraint. We derive two methods by applying the alternating direction method of multipliers (ADMM) for decentralized consensus optimization to the dual of our resource allocation problem. Both methods are fully parallelizable and decentralized in the sense that each agent exchanges information only with its neighbors in the network and requires only its own data for updating its decision. We prove convergence of the proposed methods and demonstrate their effectiveness with a numerical example.

Published
2018
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13. ADMM for Exploiting Structure in MPC Problems

Author

Rey, Felix, Hokayem, Peter, and Lygeros, John

Subjects
Mathematics - Optimization and Control
Abstract

We consider a model predictive control (MPC) setting, where we use the alternating direction method of multipliers (ADMM) to exploit problem structure. We take advantage of interacting components in the controlled system by decomposing its dynamics with virtual subsystems and virtual inputs. We introduce subsystem-individual penalty parameters together with optimal selection techniques. Further, we propose a novel measure of system structure, which we call separation tendency. For a sufficiently structured system, the resulting structure-exploiting method has the following characteristics: (i) its computational complexity scales favorably with the problem size; (ii) it is highly parallelizable; (iii) it is highly adaptable to the problem at hand; and (iv), even for a single-thread implementation, it improves the overall performance. We show a simulation study for cascade systems and compare the new method to conventional ADMM., Comment: Extended proofs, simulation details, and problem data is provided in ancillary files

Published
2018

14. Fusogenicity and neutralization sensitivity of the SARS-CoV-2 Delta sublineage AY.4.2

Author

Saunders, Nell, Planas, Delphine, Bolland, William H., Rodriguez, Christophe, Fourati, Slim, Buchrieser, Julian, Planchais, Cyril, Prot, Matthieu, Staropoli, Isabelle, Guivel-Benhassine, Florence, Porrot, Françoise, Veyer, David, Péré, Hélène, Robillard, Nicolas, Saliba, Madelina, Baidaliuk, Artem, Seve, Aymeric, Hocqueloux, Laurent, Prazuck, Thierry, Rey, Felix A., Mouquet, Hugo, Simon-Lorière, Etienne, Bruel, Timothée, Pawlotsky, Jean-Michel, and Schwartz, Olivier

Published
2022
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15. Strengthening the Group: Aggregated Frequency Reserve Bidding with ADMM

Author

Rey, Felix, Zhang, Xiaojing, Merkli, Sandro, Agliati, Valentina, Kamgarpour, Maryam, and Lygeros, John

Subjects
Mathematics - Optimization and Control
Abstract

In a power grid, the electricity supply and demand must be balanced at all times to maintain the system's frequency. In practice, the grid operator achieves this balance by procuring frequency reserves in an ahead-of-time market setting. During runtime, these reserves are then dispatched whenever there is an imbalance in the grid. Recently, there has been an increasing interest in engaging electricity consumers, such as plug-in electric vehicles or buildings, to offer such frequency reserves by exploiting their flexibility in power consumption. In this work, we focus on an aggregation of buildings that places a joint bid on a reserve market. The resulting shared decision is modeled as a large-scale optimization problem. Our main contribution is to show that the aggregation can make its decision in a computationally efficient and conceptually meaningful way, using the alternating direction method of multipliers (ADMM). The proposed approach exhibits several attractive features that include (i) the computational burden is distributed between the buildings; (ii) the setup naturally provides privacy and flexibility; (iii) the iterative algorithm can be stopped at any time, providing a feasible (though suboptimal) solution; and (iv) the algorithm provides the foundation for a reward distribution scheme that strengthens the group., Comment: New version fixes hyperlinks in document

Published
2017
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16. Modulation of SARS-CoV-2 spike binding to ACE2 through conformational selection

Author

Saha, Prithwidip, primary, Fernanadez, Ignacio, additional, Sumbul, Fidan, additional, Valotteau, Claire, additional, Kostrz, Dorota, additional, Meola, Annalisa, additional, Baquero, Eduard, additional, Sharma, Arvind, additional, Portman, James R., additional, Stransky, Francois, additional, Boudier, Thomas, additional, Guardado Calvo, Pablo, additional, Gosse, Charlie, additional, Strick, Terence, additional, Rey, Felix A., additional, and Rico, Felix, additional

Published
2024
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18. Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine

Author

Wec, Anna Z., Haslwanter, Denise, Abdiche, Yasmina N., Shehata, Laila, Pedreño-Lopez, Nuria, Moyer, Crystal L., Bornholdt, Zachary A., Lilov, Asparouh, Nett, Juergen H., Jangra, Rohit K., Brown, Michael, Watkins, David I., Ahlm, Clas, Forsell, Mattias N., Rey, Félix A., Barba-Spaeth, Giovanna, Chandran, Kartik, and Walker, Laura M.

Published
2020

19. The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human αVβ3 Integrin via Steric Hindrance

Author

Borst, Andrew J, James, Zachary M, Zagotta, William N, Ginsberg, Mark, Rey, Felix A, DiMaio, Frank, Backovic, Marija, and Veesler, David

Subjects
Biochemistry and Cell Biology, Biological Sciences, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Cancer, Amino Acid Motifs, Angiogenesis Inhibitors, Antibodies, Monoclonal, Antigens, Antiviral Agents, Binding Sites, Bone Density Conservation Agents, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli, Gene Expression, Genetic Vectors, Humans, Immunoglobulin Fab Fragments, Integrin alphaVbeta3, Ligands, Models, Molecular, Oligopeptides, Protein Binding, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Recombinant Proteins, LM609 antibody, abegrin, alpha V beta 3 integrin, etaracizumab, integrins, single-particle electron microscopy, vitaxin, Chemical Sciences, Information and Computing Sciences, Biophysics, Biological sciences, Chemical sciences
Abstract

The LM609 antibody specifically recognizes αVβ3 integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for αVβ3-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of αVβ3 integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for αVβ3. Using single-particle electron microscopy, we show that LM609 binds at the interface between the β-propeller domain of the αV chain and the βI domain of the β3 chain, near the RGD-binding site, of all observed integrin conformational states. Integrating these data with fluorescence size-exclusion chromatography, we demonstrate that LM609 sterically hinders access of large ligands to the RGD-binding pocket, without obstructing it. This work provides a structural framework to expedite future efforts utilizing LM609 as a diagnostic or therapeutic tool.

Published
2017

20. Immune correlates of protection for dengue: State of the art and research agenda

Author

Katzelnick, Leah C, Harris, Eva, Baric, Ralph, Coller, Beth-Ann, Coloma, Josefina, Crowe, James E, Cummings, Derek AT, Dean, Hansi, de Silva, Aravinda, Diamond, Michael S, Durbin, Anna, Ferguson, Neil, Gilbert, Peter B, Gordon, Aubree, Gubler, Duane J, Guy, Bruno, Halloran, M Elizabeth, Halstead, Scott, Jackson, Nicholas, Jarman, Richard, Lok, Shee-mei, Michael, Nelson L, Ooi, Eng Eong, Papadopoulos, Athanasios, Plotkin, Stanley, Precioso, Alexander R, Reiner, Robert, Rey, Felix A, Rodríguez-Barraquer, Isabel, Rothman, Alan, Schmidt, Alexander C, Screaton, Gavin, Sette, Alessandro, Simmons, Cameron, St. John, Ashley L, Sun, Wellington, Thomas, Stephen, Torresi, Joseph, Tsang, John S, Vannice, Kirsten, Whitehead, Stephen, Wilder-Smith, Annelies, and Kyu Yoon, In

Subjects
Infectious Diseases, Vector-Borne Diseases, Rare Diseases, Vaccine Related, Biodefense, Immunization, Prevention, Emerging Infectious Diseases, Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Infection, Good Health and Well Being, Antibodies, Neutralizing, Antibodies, Viral, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Congresses as Topic, Dengue, Dengue Vaccines, Dengue Virus, Humans, Severe Dengue, Dengue virus, Immune correlates of protection, Immune correlates of risk, Natural infection, Vaccine, Participants in the Summit on Dengue Immune Correlates of Protection, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
Abstract

Dengue viruses (DENV1-4) are mosquito-borne flaviviruses estimated to cause up to ∼400 million infections and ∼100 million dengue cases each year. Factors that contribute to protection from and risk of dengue and severe dengue disease have been studied extensively but are still not fully understood. Results from Phase 3 vaccine efficacy trials have recently become available for one vaccine candidate, now licensed for use in several countries, and more Phase 2 and 3 studies of additional vaccine candidates are ongoing, making these issues all the more urgent and timely. At the "Summit on Dengue Immune Correlates of Protection", held in Annecy, France, on March 8-9, 2016, dengue experts from diverse fields came together to discuss the current understanding of the immune response to and protection from DENV infection and disease, identify key unanswered questions, discuss data on immune correlates and plans for comparison of results across assays/consortia, and propose a research agenda for investigation of dengue immune correlates, all in the context of both natural infection studies and vaccine trials.

Published
2017

21. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization

Author

Planas, Delphine, Veyer, David, Baidaliuk, Artem, Staropoli, Isabelle, Guivel-Benhassine, Florence, Rajah, Maaran Michael, Planchais, Cyril, Porrot, Françoise, Robillard, Nicolas, Puech, Julien, Prot, Matthieu, Gallais, Floriane, Gantner, Pierre, Velay, Aurélie, Le Guen, Julien, Kassis-Chikhani, Najiby, Edriss, Dhiaeddine, Belec, Laurent, Seve, Aymeric, Courtellemont, Laura, Péré, Hélène, Hocqueloux, Laurent, Fafi-Kremer, Samira, Prazuck, Thierry, Mouquet, Hugo, Bruel, Timothée, Simon-Lorière, Etienne, Rey, Felix A., and Schwartz, Olivier

Published
2021
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24. A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

Author

Dejnirattisai, Wanwisa, Wongwiwat, Wiyada, Supasa, Sunpetchuda, Zhang, Xiaokang, Dai, Xinghong, Rouvinski, Alexander, Jumnainsong, Amonrat, Edwards, Carolyn, Quyen, Nguyen Than Ha, Duangchinda, Thaneeya, Grimes, Jonathan M, Tsai, Wen-Yang, Lai, Chih-Yun, Wang, Wei-Kung, Malasit, Prida, Farrar, Jeremy, Simmons, Cameron P, Zhou, Z Hong, Rey, Felix A, Mongkolsapaya, Juthathip, and Screaton, Gavin R

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Vaccine Related, Prevention, Infectious Diseases, Immunization, Biotechnology, Rare Diseases, Vector-Borne Diseases, Biodefense, Emerging Infectious Diseases, Infection, Good Health and Well Being, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Biological Assay, Cell Line, Dengue, Dengue Virus, Enzyme-Linked Immunosorbent Assay, Humans, Immunoblotting, Viral Envelope Proteins, Biochemistry and cell biology
Abstract

Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.

Published
2015

25. Viral Entry and NS1 as Potential Antiviral Drug Targets

Author

de Silva, Aravinda M., Rey, Félix A., Young, Paul R., Hilgenfeld, Rolf, Vasudevan, Subhash G., COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, REZAEI, NIMA, Series Editor, Hilgenfeld, Rolf, editor, and Vasudevan, Subhash G., editor

Published
2018
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29. Qualitative monitoring of SARS-CoV-2 mRNA vaccination in humans using droplet microfluidics

Author

Broketa, Matteo, primary, Sokal, Aurélien, additional, Mor, Michael, additional, Canales-Herrerias, Pablo, additional, Perima, Angga, additional, Meola, Annalisa, additional, Fernández, Ignacio, additional, Iannascoli, Bruno, additional, Chenon, Guilhem, additional, Vandenberghe, Alexis, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Backovic, Marija, additional, Rey, Felix A., additional, Baudry, Jean, additional, Freund, Natalia T., additional, Mahévas, Matthieu, additional, and Bruhns, Pierre, additional

Published
2023
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34. Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody

Author

Mittler, Eva, Serris, Alexandra, Esterman, Emma, Florez, Catalina, Polanco, Laura, O’brien, Cecilia, Slough, Megan, Tynell, Janne, Gröning, Remigius, Sun, Yan, Abelson, Dafna, Wec, Anna, Haslwanter, Denise, Keller, Markus, Ye, Chunyan, Bakken, Russel, Jangra, Rohit, Dye, John, Ahlm, Clas, Rappazzo, C. Garrett, Ulrich, Rainer, Zeitlin, Larry, Geoghegan, James, Bradfute, Steven, Sidoli, Simone, Forsell, Mattias N.E., Strandin, Tomas, Rey, Felix, Herbert, Andrew, Walker, Laura, Chandran, Kartik, Guardado-Calvo, Pablo, Albert Einstein College of Medicine [New York], Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Adimab [Lebanon], U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Umeå University, Mapp Biopharmaceutical Inc., Friedrich-Loeffler-Institut (FLI), The University of New Mexico [Albuquerque], Haaga-Helia University of Applied Sciences [Helsinki, Finland], This research was supported by NIAID of the NIH under award number U19AI142777 (Centers of Excellence in Translational Research) to K.C., L.M.W., J.M.D., A.S.H., S.B.B., M.N.E.F., and L.Z. M.N.E.F. was supported by a grant from the Swedish Research Council (no. 2020-06235). C.A. was supported by research grants from Region Västerbotten and Umeå University (RV-579011, RV-734361, and RV-965866). J.T. was supported by the Finnish Cultural Foundation (no. 00221066). R.K.J. was supported by grants from the NIH (R2AI156482, P20GM134974, and P20GM121307). R.G.U. was supported by the Bundesministerium für Bildung und Forschung (BMBF) within the Research Network Zoonotic Infectious Diseases (01KI1721A and 01KI2004A). T.S. was supported by the Academy of Finland (no. 321809). P.G.-C. was supported by a grant by the National French Research Agency (ANR-18-CE11-0011), and A.S. was supported with a fellowship by the French Fondation pour la Recherche Médicale (FDM20170638040). F.A.R. and P.G.-C. were supported by Labex IBEID (ANR-10-LABX-62-IBEID)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-18-CE11-0011,LISEFU,Base structurale de la détection des lipides dans la fusion virale(2018)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.

Published
2023

36. A synthetic delivery vector for mucosal vaccination

Author

Billet, Anne, primary, Hadjerci, Justine, additional, Tran, Thi, additional, Kessler, Pascal, additional, Ulmer, Jonathan, additional, Mourier, Gilles, additional, Ghazarian, Marine, additional, Gonzalez, Anthony, additional, Thai, Robert, additional, Urquia, Pauline, additional, Vanbaelen, Anne-Cecile, additional, Meola, Annalisa, additional, Fernandez, Ignacio, additional, Deville-Foillard, Stephanie, additional, MacDonald, Ewan, additional, Paolini, Lea, additional, Schmidt, Frederic, additional, Rey, Felix A, additional, Kay, Michael S, additional, Tartour, Eric, additional, Servent, Denis, additional, and Johannes, Ludger, additional

Published
2023
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39. Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination

Author

Sokal, Aurélien, primary, Bastard, Paul, additional, Chappert, Pascal, additional, Barba-Spaeth, Giovanna, additional, Fourati, Slim, additional, Vanderberghe, Alexis, additional, Lagouge-Roussey, Pauline, additional, Meyts, Isabelle, additional, Gervais, Adrian, additional, Bouvier-Alias, Magali, additional, Azzaoui, Imane, additional, Fernández, Ignacio, additional, de la Selle, Andréa, additional, Zhang, Qian, additional, Bizien, Lucy, additional, Pellier, Isabelle, additional, Linglart, Agnès, additional, Rothenbuhler, Anya, additional, Marcoux, Estelle, additional, Anxionnat, Raphael, additional, Cheikh, Nathalie, additional, Léger, Juliane, additional, Amador-Borrero, Blanca, additional, Fouyssac, Fanny, additional, Menut, Vanessa, additional, Goffard, Jean-Christophe, additional, Storey, Caroline, additional, Demily, Caroline, additional, Mallebranche, Coralie, additional, Troya, Jesus, additional, Pujol, Aurora, additional, Zins, Marie, additional, Tiberghien, Pierre, additional, Gray, Paul E., additional, McNaughton, Peter, additional, Sullivan, Anna, additional, Peake, Jane, additional, Levy, Romain, additional, Languille, Laetitia, additional, Rodiguez-Gallego, Carlos, additional, Boisson, Bertrand, additional, Gallien, Sébastien, additional, Neven, Bénédicte, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Abel, Laurent, additional, Rey, Felix A., additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, Tangye, Stuart G., additional, Casanova, Jean-Laurent, additional, and Mahévas, Matthieu, additional

Published
2022
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40. Neutralization of zoonotic retroviruses by human antibodies: genotype-specific epitopes within the receptor-binding domain from simian foamy virus

Author

Dynesen, Lasse Toftdal, primary, Fernandez, Ignacio, additional, Coquin, Youna, additional, Delaplace, Manon, additional, Montange, Thomas, additional, Njouom, Richard, additional, Bilonga-Ndongo, Chanceline, additional, Rey, Felix A., additional, Gessain, Antoine, additional, Backovic, Marija, additional, and Buseyne, Florence, additional

Published
2022
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42. Structural basis of potent Zika-dengue virus antibody cross-neutralization

Author

Barba-Spaeth, Giovanna, Dejnirattisai, Wanwisa, Rouvinski, Alexander, Vaney, Marie-Christine, Medits, Iris, Sharma, Arvind, Simon-Loriere, Etienne, Sakuntabhai, Anavaj, Cao-Lormeau, Van-Mai, Haouz, Ahmed, England, Patrick, Stiasny, Karin, Mongkolsapaya, Juthathip, Heinz, Franz X., Screaton, Gavin R., and Rey, Felix A.

Subjects
Guillain-Barre syndrome -- Research -- Health aspects, Viral antibodies -- Research -- Health aspects, Antibodies -- Research -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Zika virus is a member of the Flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in Brazil and to Guillain-Barre syndrome in adults in French Polynesia. Zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize Zika virus. The crystal structure of two of these antibodies in complex with the envelope protein of Zika virus reveals the details of a conserved epitope, which is also the site of interaction of the envelope protein dimer with the precursor membrane (prM) protein during virus maturation. Comparison of the Zika and dengue virus immunocomplexes provides a lead for rational, epitope-focused design of a universal vaccine capable of eliciting potent cross-neutralizing antibodies to protect simultaneously against both Zika and dengue virus infections., Zika virus (ZIKV) is an arthropod-borne enveloped virus belonging to the Flavivirus genus in the family Flaviviridae, which also includes the human pathogenic yellow fever, dengue, West Nile and tick-borne [...]

Published
2016
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44. Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies

Author

Engdahl, Taylor B., primary, Binshtein, Elad, additional, Brocato, Rebecca L., additional, Kuzmina, Natalia A., additional, Principe, Lucia M, additional, Kwilas, Steven A., additional, Kim, Robert K., additional, Chapman, Nathaniel S., additional, Porter, Monique S., additional, Guardado-Calvo, Pablo, additional, Rey, Felix A., additional, Handal, Laura S., additional, Diaz, Summer M., additional, Zagol-Ikapitte, Irene A., additional, Reidy, Joseph X., additional, Trivette, Andrew, additional, Bukreyev, Alexander, additional, Hooper, Jay W., additional, and Crowe, James. E., additional

Published
2022
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47. Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses

Author

Mittler, Eva, Wec, Anna Z., Tynell, Janne, Guardado-Calvo, Pablo, Wigren, Julia, Polanco, Laura C., O'Brien, Cecilia M., Slough, Megan M., Abelson, Dafna M., Serris, Alexandra, Sakharkar, Mrunal, Pehau-Arnaudet, Gerard, Bakken, Russell R., Geoghegan, James C., Jangra, Rohit K., Keller, Markus, Zeitlin, Larry, Vapalahti, Olli, Ulrich, Rainer G., Bornholdt, Zachary A., Ahlm, Clas, Rey, Felix A., Dye, John M., Bradfute, Steven B., Strandin, Tomas, Herbert, Andrew S., Forsell, Mattias N. E., Walker, Laura M., Chandran, Kartik, Mittler, Eva, Wec, Anna Z., Tynell, Janne, Guardado-Calvo, Pablo, Wigren, Julia, Polanco, Laura C., O'Brien, Cecilia M., Slough, Megan M., Abelson, Dafna M., Serris, Alexandra, Sakharkar, Mrunal, Pehau-Arnaudet, Gerard, Bakken, Russell R., Geoghegan, James C., Jangra, Rohit K., Keller, Markus, Zeitlin, Larry, Vapalahti, Olli, Ulrich, Rainer G., Bornholdt, Zachary A., Ahlm, Clas, Rey, Felix A., Dye, John M., Bradfute, Steven B., Strandin, Tomas, Herbert, Andrew S., Forsell, Mattias N. E., Walker, Laura M., and Chandran, Kartik

Abstract

The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.

Published
2022
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49. Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Author

Rouvinski, Alexander, Guardado-Calvo, Pablo, Barba-Spaeth, Giovanna, Duquerroy, Stephane, Vaney, Marie- Christine, Kikuti, Carlos M., Sanchez, M. Erika Navarro, Dejnirattisai, Wanwisa, Wongwiwat, Wiyada, Haouz, Ahmed, Girard- Blanc, Christine, Petres, Stephane, Shepard, William E., Despres, Philippe, Arenzana-Seisdedos, Fernando, Dussart, Philippe, Mongkolsapaya, Juthathip, Screaton, Gavin R., and Rey, Felix A.

Subjects
Viral antibodies -- Health aspects, Antigenic determinants -- Health aspects, Dengue viruses -- Health aspects, Antibodies -- Health aspects, Host-virus relationships -- Identification and classification, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Dengue disease is caused by four different flavivirus (1) serotypes, which infect 390 million people yearly with 25% symptomatic cases (2) and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3,4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies (5,6). We recently isolated human antibodies potently neutralizing all four dengue virus serotypes (7). Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop (8) and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell (9), explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus., Exposed at the surface of infectious mature dengue virus (DENV) particles, protein E is the sole target of neutralizing antibodies. It displays an icosahedral arrangement in which 90 E dimers [...]

Published
2015

50. Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses

Author

Mittler, Eva, primary, Wec, Anna Z., additional, Tynell, Janne, additional, Guardado-Calvo, Pablo, additional, Wigren-Byström, Julia, additional, Polanco, Laura C., additional, O’Brien, Cecilia M., additional, Slough, Megan M., additional, Abelson, Dafna M., additional, Serris, Alexandra, additional, Sakharkar, Mrunal, additional, Pehau-Arnaudet, Gerard, additional, Bakken, Russell R., additional, Geoghegan, James C., additional, Jangra, Rohit K., additional, Keller, Markus, additional, Zeitlin, Larry, additional, Vapalahti, Olli, additional, Ulrich, Rainer G., additional, Bornholdt, Zachary A., additional, Ahlm, Clas, additional, Rey, Felix A., additional, Dye, John M., additional, Bradfute, Steven B., additional, Strandin, Tomas, additional, Herbert, Andrew S., additional, Forsell, Mattias N. E., additional, Walker, Laura M., additional, and Chandran, Kartik, additional

Published
2022
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