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1. Gut microbiota in systemic lupus erythematosus patients and lupus mouse model: a cross species comparative analysis for biomarker discovery

Author

Eya Toumi, Benoit Goutorbe, Anne Plauzolles, Marion Bonnet, Soraya Mezouar, Muriel Militello, Jean-Louis Mege, Laurent Chiche, and Philippe Halfon

Subjects
systemic lupus erythematosus, gut microbiota, dysbiosis, disease activity, outcome assessment, health care, Immunologic diseases. Allergy, RC581-607
Abstract

An increasing number of studies have provided strong evidence that gut microbiota interact with the immune system and stimulate various mechanisms involved in the pathogenesis of auto-immune diseases such as Systemic Lupus Erythematosus (SLE). Indeed, gut microbiota could be a source of diagnostic and prognostic biomarkers but also hold the promise to discover novel therapeutic strategies. Thus far, specific SLE microbial signatures have not yet been clearly identified with alteration patterns that may vary between human and animal studies. In this study, a comparative analysis of a clinically well-characterized cohort of adult patients with SLE showed reduced biodiversity, a lower Firmicutes/Bacteroidetes (F/B) ratio, and six differentially abundant taxa compared with healthy controls. An unsupervised clustering of patients with SLE patients identified a subgroup of patients with a stronger alteration of their gut microbiota. Interestingly, this clustering was strongly correlated with the disease activity assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (p = 0.03, odd ratio = 15) and the identification of specific alterations involving the F/B ratio and some different taxa. Then, the gut microbiota of pristane-induced lupus and control mice were analyzed for comparison with our human data. Among the six differentially abundant taxa of the human disease signature, five were common with our murine model. Finally, an exhaustive cross-species comparison between our data and previous human and murine SLE studies revealed a core-set of gut microbiome species that might constitute biomarker panels relevant for future validation studies.

Published
2022
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2. Human Stool Preservation Impacts Taxonomic Profiles in 16S Metagenomics Studies

Author

Anne Plauzolles, Eya Toumi, Marion Bonnet, Guillaume Pénaranda, Ghislain Bidaut, Laurent Chiche, Jérôme Allardet-Servent, Frédérique Retornaz, Benoit Goutorbe, and Philippe Halfon

Subjects
microbiota, standardization, 16S metagenomics, human gut, preservation, stool, Microbiology, QR1-502
Abstract

Microbiotas play critical roles in human health, yet in most cases scientists lack standardized and reproducible methods from collection and preservation of samples, as well as the choice of omic analysis, up to the data processing. To date, stool sample preservation remains a source of technological bias in metagenomic sequencing, despite newly developed storage solutions. Here, we conducted a comparative study of 10 storage methods for human stool over a 14-day period of storage at fluctuating temperatures. We first compared the performance of each stabilizer with observed bacterial composition variation within the same specimen. Then, we identified the nature of the observed variations to determine which bacterial populations were more impacted by the stabilizer. We found that DNA stabilizers display various stabilizing efficacies and affect the recovered bacterial profiles thus highlighting that some solutions are more performant in preserving the true gut microbial community. Furthermore, our results showed that the bias associated with the stabilizers can be linked to the phenotypical traits of the bacterial populations present in the studied samples. Although newly developed storage solutions have improved our capacity to stabilize stool microbial content over time, they are nevertheless not devoid of biases hence requiring the implantation of standard operating procedures. Acknowledging the biases and limitations of the implemented method is key to better interpret and support true associated microbiome patterns that will then lead us towards personalized medicine, in which the microbiota profile could constitute a reliable tool for clinical practice.

Published
2022
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3. Targeting human langerin promotes HIV-1 specific humoral immune responses.

Author

Jérôme Kervevan, Aurélie Bouteau, Juliane S Lanza, Adele Hammoudi, Sandra Zurawski, Mathieu Surenaud, Lydie Dieudonné, Marion Bonnet, Cécile Lefebvre, Hakim Hocini, Romain Marlin, Aurélie Guguin, Barbara Hersant, Oana Hermeziu, Elisabeth Menu, Christine Lacabaratz, Jean-Daniel Lelièvre, Gerard Zurawski, Véronique Godot, Sandrine Henri, Botond Z Igyártó, Yves Levy, and Sylvain Cardinaud

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

The main avenue for the development of an HIV-1 vaccine remains the induction of protective antibodies. A rationale approach is to target antigen to specific receptors on dendritic cells (DC) via fused monoclonal antibodies (mAb). In mouse and non-human primate models, targeting of skin Langerhans cells (LC) with anti-Langerin mAbs fused with HIV-1 Gag antigen drives antigen-specific humoral responses. The development of these immunization strategies in humans requires a better understanding of early immune events driven by human LC. We therefore produced anti-Langerin mAbs fused with the HIV-1 gp140z Envelope (αLC.Env). First, we show that primary skin human LC and in vitro differentiated LC induce differentiation and expansion of naïve CD4+ T cells into T follicular helper (Tfh) cells. Second, when human LC are pre-treated with αLC.Env, differentiated Tfh cells significantly promote the production of specific IgG by B cells. Strikingly, HIV-Env-specific Ig are secreted by HIV-specific memory B cells. Consistently, we found that receptors and cytokines involved in Tfh differentiation and B cell functions are upregulated by LC during their maturation and after targeting Langerin. Finally, we show that subcutaneous immunization of mice by αLC.Env induces germinal center (GC) reaction in draining lymph nodes with higher numbers of Tfh cells, Env-specific B cells, as well as specific IgG serum levels compared to mice immunized with the non-targeting Env antigen. Altogether, we provide evidence that human LC properly targeted may be licensed to efficiently induce Tfh cell and B cell responses in GC.

Published
2021
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5. UK CTAP Briefing on Ivermectin - National Core Studies

Author

Marion Bonnet, Alison Cave, Matthias P Hofer, Glenn A McConkey, Nicholas Medcalf, Stephen P Smith, Teresa Tsakok, Robert Watson, Steve Webster, and Tao You

Subjects
COVID-19, Ivermectin, Therapeutics, Clinical Trials, National Core Studies
Abstract

The UK COVID-19 Therapeutics Advisory Panel was convened to review and select potential COVID-19 therapeutics for publicly funded clinical trials. Briefs were prepared by the UKRI Secretariat Due Diligence Team to support the work of the Panel. The aim of briefs was to summarise and qualify the evidence for candidate drugs proposed by industry, academia and the general public through an open portal. Briefs were prepared rapidly to meet tight deadlines in response to the COVID-19 pandemic. They reflect the state of knowledge regarding COVID-19 and drug candidate at the date of completion (Chinnery et al., 2021). This brief is published for transparency and historical record and should not be understood as a peer reviewed scientific publication. The date of completion is marked and it is redacted where commercial sensitivities are involved

Published
2022
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6. Choosing drugs for UK COVID-19 treatment trials

Author

Patrick F. Chinnery, Marion Bonnet, Alison Cave, Matthias P. Hofer, Alastair Lamb, Glenn A. McConkey, Nicholas Medcalf, Stephen P. Smith, Teresa Tsakok, Robert Watson, Steve Webster, and Tao You

Subjects
Pharmacology, Drug Discovery, General Medicine
Abstract

In 2020, the UK government funded a portfolio of platform trials to develop new treatments for COVID-19. A key feature was the independent prioritization of candidate drugs with central coordination to prevent duplication, accelerating recruitment to deliver definitive trial results. A similar approach could be used for non-communicable diseases where treatment advances have been limited.

Published
2021

7. Small Intestinal Bacterial Overgrowths and Intestinal Methanogen Overgrowths Breath Testing in a Real-Life French Cohort

Author

Anne, Plauzolles, Stella, Uras, Guillaume, Pénaranda, Marion, Bonnet, Patrick, Dukan, Frédérique, Retornaz, and Philippe, Halfon

Subjects
Gastroenterology
Abstract

Breath testing has become a widely used tool to diagnose small intestinal bacterial overgrowths (SIBO) and intestinal methanogen overgrowths (IMO) in clinical settings. Due to the heterogeneity in clinical manifestations and lack of standardization among centers performing breath testing, SIBO and IMO can be easily overlooked by the clinician.We studied the prevalence and symptoms of SIBO/IMO in French patients referred for breath testing after seeking medical advice.Breath test data and symptoms of 331 patients were assessed for SIBO/IMO using the H2/CH4 lactulose breath test (LBT). Wilcoxon test or χ2 test were used to compare patients with SIBO/IMO to patients without SIBO/IMO. LBT positive patients (H2+, CH4+, and CH4+/H2+) were compared using Kruskal-Wallis test for continuous data or χ2 test for categorical data.Among the 186 (68.1%) patients tested positive for an overgrowth with respectively 40.3%, 47.3%, 12.4% for H2+, CH4+ and CH4+/H2+, presence of diarrhea was significantly increased in hydrogen type overgrowths (p0.001). No significant difference according to age, gender and symptoms was associated with a positive test except for joint pain that was less prevalent among LBT positive patients (p=0.038). In 86.5% of IMOs, positivity with CH4 values ≥10ppm could be identified at baseline.There are little discriminating symptoms that can help the clinician to identify patients likely to have a SIBO/IMO. However, SIBO/IMOs remain a common disorder widely underdiagnosed that need further studies to better apprehend functional bowel disorders.

Published
2022
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9. Human stool preservation impacts taxonomic profiles in 16S rRNA gene-based metagenomics studies

Author

Jérôme Allardet-Servent, Laurent Chiche, Frédérique Retornaz, Anne Plauzolles, Philippe Halfon, Ghislain Bidaut, Eya Toumi, Guillaume Penaranda, Benoit Goutorbe, and Marion Bonnet

Subjects
Metagenomics, Computational biology, Biology, 16S ribosomal RNA, Gene
Abstract

Background: Microbiotas play critical roles in human health, yet in most cases scientists lack standardized and reproducible methods. To date, stool sample preservation remains a source of technological bias in metagenomic sequencing, despite newly developed storage solutions. Studying those biases will help in identifying the appropriate stool preservation approach to promote the implementation of standard operating procedure and improve comparability across multiple microbiome studies. Results: Here, we conducted a comparative study of 10 storage methods for human stool over a 15-day period of storage at fluctuating temperatures. We first compared the performance of each stabilizer with observed bacterial composition variation within the same specimen. Then, we identified the nature of the observed variations to determine which bacterial populations were more impacted by the stabilizer. We found that DNA stabilizers display various stabilizing efficacies and affect the recovered bacterial profiles. Furthermore, our results showed that the bias associated with the stabilizers can be linked to the phenotypical characteristics of the bacterial populations present in the studied samples. Conclusions: Although newly developed storage solutions have improved our capacity to stabilize stool microbial content over time, they are nevertheless not devoid of biases. We therefore recommend considering the nature of these technological biases before claiming whether some microbes are beneficial or even deleterious to human health.

Published
2020
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10. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trialsResearch in context

Author

Ilias I. Siempos, Andre C. Kalil, Drifa Belhadi, Viviane Cordeiro Veiga, Alexandre Biasi Cavalcanti, Westyn Branch-Elliman, Eleni Papoutsi, Konstantinos Gkirgkiris, Nikoleta A. Xixi, Anastasia Kotanidou, Olivier Hermine, Raphaël Porcher, Xavier Mariette, Philippe Ravaud, Serge Bureau, Maxime Dougados, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Annick Tibi, Elie Azoulay, Jacques Cadranel, Joseph Emmerich, Muriel Fartoukh, Bertrand Guidet, Marc Humbert, Karine Lacombe, Matthieu Mahevas, Frédéric Pene, Valerie Pourchet-Martinez, Frédéric Schlemmer, Yazdan Yazdanpanah, Gabriel Baron, Elodie Perrodeau, Damien Vanhoye, Cécile Kedzia, Lauren Demerville, Anne Gysembergh-Houal, Alexandre Bourgoin, Nabil Raked, Lakhdar Mameri, Claire Montlahuc, Lucie Biard, St.phanie Alary, Samir Hamiria, Thinhinane Bariz, Hala Semri, Dhiaa Meriem Hai, Moustafa Benafla, Mohamed Belloul, Pernelle Vauboin, Saskia Flamand, Claire Pacheco, Anouk Walter-Petrich, Emilia Stan, Souad Benarab, Corine Nyanou, Robin Charreteur, Céline Dupre, Kévin Cardet, Blandine Lehmann, Kamyl Baghli, Claire Madelaine, Eric D'Ortenzio, Oriane Puéchal, Caroline Semaille, Laurent Savale, Anatole Harrois, Samy Figueiredo, Jacques Duranteau, Nadia Anguel, Arthur Pavot, Xavier Monnet, Christian Richard, Jean-Louis Teboul, Philippe Durand, Pierre Tissieres, Mitja Jevnikar, David Montani, Stephan Pavy, Gaétane Nocturne, Samuel Bitoun, Nicolas Noel, Olivier Lambotte, Lelia Escaut, Stephane Jauréguiberry, Elodie Baudry, Christiane Verny, Edouard Lefevre, Mohamad Zaidan, Domitille Molinari, Gaël Leprun, Alain Fourreau, Laurent Cylly, Lamiae Grimaldi, Myriam Virlouvet, Ramdane Meftali, Soléne Fabre, Marion Licois, Asmaa Mamoune, Yacine Boudali, Clotilde Le Tiec, Céline Verstuyft, Anne-Marie Roques, Sophie Georgin-Lavialle, Patricia Senet, Gilles Pialoux, Angele Soria, Antoine Parrot, Helene François, Nathalie Rozensztajn, Emmanuelle Blin, Pascaline Choinier, Juliette Camuset, Jean-Simon Rech, Antony Canellas, Camille Rolland-Debord, Nadege Lemarié, Nicolas Belaube, Marine Nadal, Martin Siguier, Camille Petit-Hoang, Julie Chas, Elodie Drouet, Matthieu Lemoine, Audrey Phibel, Lucie Aunay, Eliane Bertrand, Sylviane Ravato, Marie Vayssettes, Anne Adda, Celine Wilpotte, Pélagie Thibaut, Julie Fillon, Isabelle Debrix, Soraya Fellahi, Jean-Philippe Bastard, Guillaume Lefévre, Jacques-Eric Gottenberg, Yves Hansmann, Frédéric Blanc, Sophie Ohlmann-Caillard, Vincent Castelain, Emmanuel Chatelus, Eva Chatron, Olivier Collange, François Danion, Frédéric De Blay, Pierre Diemunsch, Sophie Diemunsch, Renaud Felten, Bernard Goichot, Valentin Greigert, Aurelien Guffroy, Bob Heger, Charlotte Kaeuffer, Loic Kassegne, Anne Sophie Korganow, Pierrick Le Borgne, Nicolas Lefebvre, Paul-Michel Mertes, Eric Noll, Mathieu Oberlin, Vincent Poindron, Julien Pottecher, Yvon Ruch, François Weill, Nicolas Meyer, Emmanuel Andres, Eric Demonsant, Hakim Tayebi, Gabriel Nisand, Stéphane Brin, Cédric Sublon, Guillaume Becker, Anne Hutt, Tristan Martin, Sophie Bayer, Catherine Metzger, Arsene Mekinian, Noémie Abisror, Amir Adedjouma, Diane Bollens, Marion Bonneton, Nathalie Bourcicaux, Anne Bourrier, Maria Chauchard Thibault Chiarabiani, Doroth.e Chopin, Jonathan Cohen, Ines Devred, Bruno Donadille, Olivier Fain, Geoffrey Hariri, Vincent Jachiet, Patrick Ingliz, Marc Garnier, Marc Gatfosse, Etienne Ghrenassia, Delphine Gobert, Jessica Krause le Garrec, Cecilia Landman, Jean Remy Lavillegrand, Benedicte Lefebvre, Thibault Mahevas, Sandie Mazerand, Jean Luc Meynard, Marjolaine Morgand, Zineb Ouaz.ne, Jerome Pacanowski, S.bastien Riviere, Philippe Seksik, Harry Sokol, Heithem Soliman, Nadia Valin, Thomas Urbina, Chloé McAvoy, Maria Pereira Miranda, Gladys Aratus, Laurence Berard, Tabassome Simon, Anne Daguenel Nguyen, Elise Girault, Cl.mentine Mayala-Kanda, Marie Antignac, Céline Leplay, Jean-Benoit Arlet, Jean-Luc Diehl, Florence Bellenfant, Anne Blanchard, Alexandre Buffet, Bernard Cholley, Antoine Fayol, Edouard Flamarion, Anne Godier, Thomas Gorget, Sophie-Rym Hamada, Caroline Hauw-Berlemont, Jean-Sébastien Hulot, David Lebeaux, Marine Livrozet, Adrien Michon, Arthur Neuschwander, Marie-Aude Pennet, Benjamin Planquette, Brigitte Ranque, Olivier Sanchez, Geoffroy Volle, Sandrine Briois, Mathias Cornic, Virginie Elisee, Jesuthasan Denis, Juliette Djadi-Prat, Pauline Jouany, Ramon Junquera, Mickael Henriques, Amina Kebir, Isabelle Lehir, Jeanne Meunier, Florence Patin, Val.rie Paquet, Anne Tréhan, Véronique Vigna, Brigitte Sabatier, Damien Bergerot, Charléne Jouve, Camille Knosp, Olivia Lenoir, Nassim Mahtal, Léa Resmini, Xavier Lescure, Jade Ghosn, Antoine Bachelard, Anne Rachline, Valentina Isernia, Bao-chau, Phung, Dorothée Vallois, Aurelie Sautereau, Catherine Neukrich, Antoine Dossier, Raphaël Borie, Bruno Crestani, Gregory Ducrocq, Philippe Gabriel Steg, Philippe Dieude, Thomas Papo, Estelle Marcault, Marhaba Chaudhry, Charléne Da Silveira, Annabelle Metois, Ismahan Mahenni, Meriam Meziani, Cyndie Nilusmas, Sylvie Le Gac, Awa Ndiaye, Fran.oise Louni, Malikhone Chansombat, Zelie Julia, Solaya Chalal, Lynda Chalal, Laura Kramer, Jeniffer Le Grand, Kafif Ouifiya, Valentine Piquard, Sarah Tubiana, Yann Nguyen, Vasco Honsel, Emmanuel Weiss, Anais Codorniu, Virginie Zarrouk, Victoire de Lastours, Matthieu Uzzan, Naura Gamany, Agathe Claveirole, Alexandre Navid, Tiffanie Fouque, Yonathan Cohen, Maya Lupo, Constance Gilles, Roza Rahli, Zeina Louis, David Boutboul, Lionel Galicier, Yaël Amara, Gabrielle Archer, Amira Benattia, Anne Bergeron, Louise Bondeelle, Nathalie de Castro, Melissa Clément, Michaël Darmon, Blandine Denis, Clairelyne Dupin, Elsa Feredj, Delphine Feyeux, Adrien Joseph, Etienne Lenglin, Pierre Le Guen, Geoffroy Liégeon, Gwenaël Lorillon, Asma Mabrouki, Eric Mariotte, Grégoire Martin de Frémont, Adrien Mirouse, Jean-Michel Molina, Régis Peffault de Latour, Eric Oksenhendler, Julien Saussereau, Abdellatif Tazi, Jean-Jacques Tudesq, Lara Zafrani, Isabelle Brindele, Emmanuelle Bugnet, Karine Celli Lebras, Julien Chabert, Lamia Djaghout, Catherine Fauvaux, Anne Lise Jegu, Ewa Kozakiewicz, Martine Meunier, Marie-Thérèse Tremorin, Claire Davoine, Isabelle Madelaine, Sophie Caillat-Zucman, Constance Delaugerre, Florence Morin, Damien Sène, Ruxandra Burlacu, Benjamin Chousterman, Bruno Mégarbanne, Pascal Richette, Jean-Pierre Riveline, Aline Frazier, Eric Vicaut, Laure Berton, Tassadit Hadjam, Miguel Alejandro Vazquez-Ibarra, Clément Jourdaine, Olivia Tran, Véronique Jouis, Aude Jacob, Julie Smati, Stéphane Renaud, Claire Pernin, Lydia Suarez, Luca Semerano, Sébastien Abad, Ruben B. nainous, Nicolas Bonnet, Celine Comparon, Yves Cohen, Hugues Cordel, Robin Dhote, Nathalie Dournon, Boris Duchemann, Nathan Ebstein, Thomas Gille, Benedicte Giroux-Leprieur, Jeanne Goupil de Bouille, Hilario Nunes, Johanna Oziel, Dominique Roulot, Lucile Sese, ClaireTantet, Yurdagul Uzunhan, Coralie Bloch-Queyrat, Vincent Levy, Fadhila Messani, Mohammed Rahaoui, Myléne Petit, Sabrina Brahmi, Vanessa Rathoin, Marthe Rigal, Nathalie Costedoat-Chalumeau, Liem Binh Luong, Zakaria Ait Hamou, Sarah Benghanem, Philippe Blanche, Nicolas Carlier, Benjamin Chaigne, Remy Gauzit, Hassan Joumaa, Mathieu Jozwiak, Marie Lachétre, Hélène Lafoeste, Odie Launay, Paul Legendre, Jonathan Marey, Caroline Morbieu, Lola-Jade Palmieri, Tali-Anne Szwebel, Hendy Abdoul, Alexandra Bruneau, Audrey Beclin-Clabaux, Charly Larrieu, Pierre Montanari, Eric Dufour, Ada Clarke, Catherine Le Bourlout, Nathalie Marin, Nathalie Menage, Samira Saleh-Mghir, Mamadou Salif Cisse, Kahina Cheref, Corinne Guerin, Jérémie Zerbit, Marc Michel, Sébastien Gallien, Etienne Crickx, Benjamin Le Vavasseur, Emmanuelle Kempf, Karim Jaffal, William Vindrios, Julie Oniszczuk, Constance Guillaud, Pascal Lim, Elena Fois, Giovanna Melica, Marie Matignon, Maud Jalabert, Jean-Daniel Lelièvre, David Schmitz, Marion Bourhis, Sylia Belazouz, Laetitia Languille, Caroline Boucle, Nelly Cita, Agnés Didier, Fahem Froura, Katia Ledudal, Thiziri Sadaoui, Alaki Thiemele, Delphine Le Febvre De Bailly, Muriel Carvhalo Verlinde, Julien Mayaux, Patrice Cacoub, David Saadoun, Mathieu Vautier, Héléne Bugaut, Olivier Benveniste, Yves Allenbach, Gaëlle Leroux, Aude Rigolet, Perrine Guillaume-Jugnot, Fanny Domont, Anne Claire Desbois, Chloé Comarmond, Nicolas Champtiaux, Segolene Toquet, Amine Ghembaza, Matheus Vieira, Georgina Maalouf, Goncalo Boleto, Yasmina Ferfar, Jean-Christophe Corvol, C.line Louapre, Sara Sambin, Louise-Laure Mariani, Carine Karachi, Florence Tubach, Candice Estellat, Linda Gimeno, Karine Martin, Aicha Bah, Vixra Keo, Sabrine Ouamri, Yasmine Messaoudi, Nessima Yelles, Pierre Faye, Sebastien Cavelot, Cecile Larcheveque, Laurence Annonay, Jaouad Benhida, Aida Zahrate-Ghoul, Soumeya Hammal, Ridha Belilita, Fanny Charbonnier, Claire Aguilar, Fanny Alby-Laurent, Carole Burger, Clara Campos-Vega, Nathalie Chavarot, Benjamin Fournier, Claire Rouzaud, Damien Vimpére, Caroline Elie, Prissile Bakouboula, Laure Choupeaux, Sophie Granville, Elodie Issorat, Christine Broissand, Marie-Alexandra Alyanakian, Guillaume Geri, Nawal Derridj, Naima Sguiouar, Hakim Meddah, Mourad Djadel, Héléne Chambrin-Lauvray, Jean-Charles Duclos-vallée, Faouzi Saliba, Sophie-Caroline Sacleux, Ilias Kounis, Sonia Tamazirt, Eric Rudant, Jean-Marie Michot, Annabelle Stoclin, Emeline Colomba, Fanny Pommeret, Christophe Willekens, Rosa Da Silva, Valérie Dejean, Yasmina Mekid, Ines Ben-Mabrouk, Florence Netzer, Caroline Pradon, Laurence Drouard, Valérie Camara-Clayette, Alexandre Morel, Gilles Garcia, Abolfazl Mohebbi, Férial Berbour, Mélanie Dehais, Anne-Lise Pouliquen, Alison Klasen, Loren Soyez-Herkert, Jonathan London, Younes Keroumi, Emmanuelle Guillot, Guillaume Grailles, Younes El amine, Fanny Defrancq, Hanane Fodil, Chaouki Bouras, Dominique Dautel, Nicolas Gambier, Thierno Dieye, Boris Bienvenu, Victor Lancon, Laurence Lecomte, Kristina Beziriganyan, Belkacem Asselate, Laure Allanic, Elena Kiouris, Marie-Héléne Legros, Christine Lemagner, Pascal Martel, Vincent Provitolo, Félix Ackermann, Mathilde Le Marchand, Aurélie Chan Hew Wai, Dimitri Fremont, Elisabeth Coupez, Mireille Adda, Frédéric Duée, Lise Bernard, Antoine Gros, Estelle Henry, Claire Courtin, Anne Pattyn, Pierre-Grégoire Guinot, Marc Bardou, Agnes Maurer, Julie Jambon, Amélie Cransac, Corinne Pernot, Bruno Mourvillier, Eric Marquis, Philippe Benoit, Damien Roux, Coralie Gernez, Cécile Yelnik, Julien Poissy, Mandy Nizard, Fanette Denies, Helene Gros, Jean-Jacques Mourad, Emmanuelle Sacco, Sophie Renet, F. Ader, Y. Yazdanpanah, F. Mentre, N. Peiffer-Smadja, F.X. Lescure, J. Poissy, L. Bouadma, J.F. Timsit, B. Lina, F. Morfin-Sherpa, M. Bouscambert, A. Gaymard, G. Peytavin, L. Abel, J. Guedj, C. Andrejak, C. Burdet, C. Laouenan, D. Belhadi, A. Dupont, T. Alfaiate, B. Basli, A. Chair, S. Laribi, J. Level, M. Schneider, M.C. Tellier, A. Dechanet, D. Costagliola, B. Terrier, M. Ohana, S. Couffin-Cadiergues, H. Esperou, C. Delmas, J. Saillard, C. Fougerou, L. Moinot, L. Wittkop, C. Cagnot, S. Le Mestre, D. Lebrasseur-Longuet, V. Petrov-Sanchez, A. Diallo, N. Mercier, V. Icard, B. Leveau, S. Tubiana, B. Hamze, A. Gelley, M. Noret, E. D’Ortenzio, O. Puechal, C. Semaille, T. Welte, J.A. Paiva, M. Halanova, M.P. Kieny, E. Balssa, C. Birkle, S. Gibowski, E. Landry, A. Le Goff, L. Moachon, C. Moins, L. Wadouachi, C. Paul, A. Levier, D. Bougon, F. Djossou, L. Epelboin, J. Dellamonica, C.H. Marquette, C. Robert, S. Gibot, E. Senneville, V. Jean-Michel, Y. Zerbib, C. Chirouze, A. Boyer, C. Cazanave, D. Gruson, D. Malvy, P. Andreu, J.P. Quenot, N. Terzi, K. Faure, C. Chabartier, V. Le Moing, K. Klouche, T. Ferry, F, Valour, B. Gaborit, E. Canet, P. Le Turnier, D. Boutoille, F. Bani-Sadr, F. Benezit, M. Revest, C. Cameli, A. Caro, MJ Ngo Um Tegue, Y. Le Tulzo, B. Laviolle, F. Laine, G. Thiery, F. Meziani, Y. Hansmann, W. Oulehri, C. Tacquard, F. Vardon-Bounes, B. Riu-Poulenc, M. Murris-Espin, L. Bernard, D. Garot, O. Hinschberger, M. Martinot, C. Bruel, B. Pilmis, O. Bouchaud, P. Loubet, C. Roger, X. Monnet, S. Figueiredo, V. Godard, J.P. Mira, M. Lachatre, S. Kerneis, J. Aboab, N. Sayre, F. Crockett, D. Lebeaux, A. Buffet, J.L. Diehl, A. Fayol, J.S. Hulot, M. Livrozet, A Mekontso- Dessap, C. Ficko, F. Stefan, J. Le Pavec, J. Mayaux, H. Ait-Oufella, J.M. Molina, G. Pialoux, M. Fartoukh, J. Textoris, M. Brossard, A. Essat, E. Netzer, Y. Riault, M. Ghislain, L. Beniguel, M. Genin, L. Gouichiche, C. Betard, L. Belkhir, A. Altdorfer, V Fraipont Centro, S. Braz, JM Ferreira Ribeiro, R Roncon Alburqueque, M. Berna, M. Alexandre, B. Lamprecht, A. Egle, R. Greil, M. Joannidis, Thomas F. Patterson, Philip O. Ponce, Barbara S. Taylor, Jan E. Patterson, Jason E. Bowling, Heta Javeri, LuAnn Larson, Angela Hewlett, Aneesh K. Mehta, Nadine G. Rouphael, Youssef Saklawi, Nicholas Scanlon, Jessica J. Traenkner, Ronald P. Trible, Jr., Emmanuel B. Walter, Noel Ivey, Thomas L. Holland, Guillermo M. Ruiz-Palacios, Alfredo Ponce de León, Sandra Rajme, Lanny Hsieh, Alpesh N. Amin, Miki Watanabe, Helen S. Lee, Susan Kline, Joanne Billings, Brooke Noren, Hyun Kim, Tyler D. Bold, Victor Tapson, Jonathan Grein, Fayyaz Sutterwala, Nicole Iovine, Lars K. Beattie, Rebecca Murray Wakeman, Matthew Shaw, Mamta K. Jain, Satish Mocherla, Jessica Meisner, Amneris Luque, Daniel A. Sweeney, Constance A. Benson, Farhana Ali, Robert L. Atmar, Hana M. El Sahly, Jennifer Whitaker, Ann R. Falsey, Angela R. Branche, Cheryl Rozario, Justino Regalado Pineda, José Arturo Martinez-Orozco, David Chien Lye, Sean WX. Ong, Po Ying Chia, Barnaby E. Young, Uriel Sandkovsky, Mezgebe Berhe, Clinton Haley, Emma Dishner, Valeria D. Cantos, Colleen F. Kelley, Paulina A. Rebolledo Esteinou, Sheetal Kandiah, Sarah B. Doernberg, Pierre-Cedric B. Crouch, Hannah Jang, Anne F. Luetkemeyer, Jay Dwyer, Stuart H. Cohen, George R. Thompson, 3rd, Hien H. Nguyen, Robert W. Finberg, Jennifer P. Wang, Juan Perez-Velazquez, Mireya Wessolossky, Patrick E.H. Jackson, Taison D. Bell, Miranda J. West, Babafemi Taiwo, Karen Krueger, Johnny Perez, Triniece Pearson, Catharine I. Paules, Kathleen G. Julian, Danish Ahmad, Alexander G. Hajduczok, Henry Arguinchona, Christa Arguinchona, Nathaniel Erdmann, Paul Goepfert, Neera Ahuja, Maria G. Frank, David Wyles, Heather Young, Myoung-don Oh, Wan Beom Park, Chang Kyung Kang, Vincent Marconi, Abeer Moanna, Sushma Cribbs, Telisha Harrison, Eu Suk Kim, Jongtak Jung, Kyoung-Ho Song, Hong Bin Kim, Seow Yen Tan, Humaira Shafi, MF Jaime Chien, Raymond KC. Fong, Daniel D. Murray, Jens Lundgren, Henrik Nielsen, Tomas Jensen, Barry S. Zingman, Robert Grossberg, Paul F. Riska, Otto O. Yang, Jenny Ahn, Rubi Arias, Rekha R. Rapaka, Naomi Hauser, James D. Campbell, William R. Short, Pablo Tebas, Jillian T. Baron, Susan L.F. McLellan, Lucas S. Blanton, Justin B. Seashore, C. Buddy Creech, Todd W. Rice, Shannon Walker, Isaac P. Thomsen, Diego Lopez de Castilla, Jason W. Van Winkle, Francis X. Riedo, Surinder Kaur Pada, Alvin DY. Wang, Li Lin, Michelle Harkins, Gregory Mertz, Nestor Sosa, Louis Yi Ann Chai, Paul Anantharajah Tambyah, Sai Meng Tham, Sophia Archuleta, Gabriel Yan, David A. Lindholm, Ana Elizabeth Markelz, Katrin Mende, Richard Mularski, Elizabeth Hohmann, Mariam Torres-Soto, Nikolaus Jilg, Ryan C. Maves, Gregory C. Utz, Sarah L. George, Daniel F. Hoft, James D. Brien, Roger Paredes, Lourdes Mateu, Cora Loste, Princy Kumar, Sarah Thornton, Sharmila Mohanraj, Noreen A. Hynes, Lauren M. Sauer, Christopher J. Colombo, Christina Schofield, Rhonda E. Colombo, Susan E. Chambers, Richard M. Novak, Andrea Wendrow, Samir K. Gupta, Tida Lee, Tahaniyat Lalani, Mark Holodniy, Aarthi Chary, Nikhil Huprikar, Anuradha Ganesan, Norio Ohmagari, Ayako Mikami, D. Ashley Price, Christopher J.A. Duncan, Kerry Dierberg, Henry J. Neumann, Stephanie N. Taylor, Alisha Lacour, Najy Masri, Edwin Swiatlo, Kyle Widmer, James D. Neaton, Mary Bessesen, David S. Stephens, Timothy H. Burgess, Timothy M. Uyeki, Robert Walker, G. Lynn Marks, Anu Osinusi, Huyen Cao, Anabela Cardoso, Stephanie de Bono, Douglas E. Schlichting, Kevin K. Chung, Jennifer L. Ferreira, Michelle Green, Mat Makowski, Michael R. Wierzbicki, Tom M. Conrad, Jill Ann El-Khorazaty, Heather Hill, Tyler Bonnett, Nikki Gettinger, Theresa Engel, Teri Lewis, Jing Wang, John H. Beigel, Kay M. Tomashek, Varduhi Ghazaryan, Tatiana Beresnev, Seema Nayak, Lori E. Dodd, Walla Dempsey, Effie Nomicos, Marina Lee, Rhonda Pikaart-Tautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Tammy Yokum, Janice Arega, Ruth Florese, Jocelyn D. Voell, Richard Davey, Ruth C. Serrano, Zanthia Wiley, Varun K. Phadke, Paul A. Goepfert, Carlos A. Gomez, Theresa A. Sofarelli, Laura Certain, Hannah N. Imlay, Cameron R. Wolfe, Emily R. Ko, John J. Engemann, Nora Bautista Felix, Claire R. Wan, Sammy T. Elmor, Laurel R. Bristow, Michelle S. Harkins, Nicole M. Iovine, Marie-Carmelle Elie-Turenne, Victor F. Tapson, Pyoeng Gyun Choe, Richard A. Mularski, Kevin S. Rhie, Rezhan H. Hussein, Dilek Ince, Patricia L. Winokur, Jin Takasaki, Sho Saito, Kimberly McConnell, PharmD, David L. Wyles, Ellen Sarcone, Kevin A. Grimes, Katherine Perez, Charles Janak, Jennifer A. Whitaker, Paulina A. Rebolledo, John Gharbin, Allison A. Lambert, Diego F. Zea, Emma Bainbridge, David C. Hostler, Jordanna M. Hostler, Brian T. Shahan, Evelyn Ling, Minjoung Go, Fleesie A. Hubbard, Melony Chakrabarty, Maryrose Laguio-Vila, Edward E. Walsh, Faheem Guirgis, Vincent C. Marconi, Christian Madar, Scott A. Borgetti, Corri Levine, Joy Nock, Keith Candiotti, Julia Rozman, Fernando Dangond, Yann Hyvert, Andrea Seitzinger, Kaitlyn Cross, Stephanie Pettibone, Seema U. Nayak, and Gregory A. Deye

Subjects
Acute respiratory distress syndrome, Acute hypoxemic respiratory failure, Pneumonia, Critically ill, Cancer, Medicine (General), R5-920
Abstract

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Published
2024
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11. Factors associated with COVID-19 vaccine uptake among French population aged 65 years and older: results from a national online survey

Author

Yu-Jin Jung, Amandine Gagneux-Brunon, Marion Bonneton, Elisabeth Botelho-Nevers, Pierre Verger, Jeremy K. Ward, and Odile Launay

Subjects
Vaccination intention, COVID-19, Pandemic, Geriatrics, RC952-954.6
Abstract

Abstract Background In France, the increase in COVID-19 vaccine uptake among older adults slowed down between May and June 2021. Using the data from a national survey, we aimed to assess COVID-19 vaccine uptake among French residents aged 65 years and older, particularly at risk of severe form of the infection, and identify factors associated with non-vaccination. Methods A cross-sectional online survey collected the immunization status/intention to get the COVID-19 vaccine, reasons for vaccination/non-vaccination and factors potentially associated with vaccine uptake between May 10 and 23, 2021 among a large sample of French residents. Characteristics of participants were compared according to immunization status. Factors potentially associated with non-vaccination were computed into a multivariate logistic regression. Results Among the 1941 survey participants, 1612 (83%) reported having received at least one dose of COVID-19 vaccine. Among the 329 unvaccinated, 197 (60%) declared having the intention to get vaccinated. Younger age (adjusted odds ratio (aOR) = 1.50; 95% confidence interval (CI), 1.05–2.14), thinking previously having COVID-19 (aOR = 4.01; 95% CI, 2.17–7.40), having suffered economic impact due to the pandemic (aOR = 2.63; 95% CI, 1.71–4.04), reporting an “unsafe” opinion about COVID-19 vaccine safety (aOR = 6.79; 95% CI, 4.50–10.26), reporting an “unsupportive” opinion about vaccination in general (aOR = 4.24; 95% CI, 2.77–6.49) were independent risk factors for non-vaccination. On the other hand, trust in COVID-19 vaccine information delivered by the doctor (aOR = 0.28; 95% CI, 0.16–0.48) and trust in the government’s actions (aOR = 0.50; 95% CI, 0.34–0.74) were independent protective factors for non-vaccination. Political affiliation also remained significantly associated with vaccine uptake. Conclusions Despite high overall COVID-19 vaccine uptake among the study participants, differences in vaccine uptake according to the level of concerns regarding COVID-19 vaccine safety, socioeconomic profile and trust in the government were observed. Our results reinforce the importance of “reaching out” vaccination strategy that specifically targets the most vulnerable fringe of older adult population.

Published
2022
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12. Pyogenic Bacterial Infections in Humans with IRAK-4 Deficiency

Author

Capucine Picard, Anne Puel, Marion Bonnet, Cheng-Lung Ku, Jacinta Bustamante, Kun Yang, Claire Soudais, Stéphanie Dupuis, Jacqueline Feinberg, Claire Fieschi, Carole Elbim, Remi Hitchcock, David Lammas, Graham Davies, Abdulaziz Al-Ghonaium, Hassan Al-Rayes, Sulaiman Al-Jumaah, Sami Al-Hajjar, Ibrahim Zaid Al-Mohsen, Husn H. Frayha, Rajivi Rucker, Thomas R. Hawn, Alan Aderem, Haysam Tufenkeji, Soichi Haraguchi, Noorbibi K. Day, Robert A. Good, Marie-Anne Gougerot-Pocidalo, Adrian Ozinsky, and Jean-Laurent Casanova

Subjects
Lipopolysaccharides, Male, Neutrophils, Receptors, Cell Surface, Monocytes, Pneumococcal Infections, Drosophila Proteins, Humans, Child, Alleles, Membrane Glycoproteins, Multidisciplinary, Tumor Necrosis Factor-alpha, Interleukins, Toll-Like Receptors, Receptors, Interleukin-1, Receptors, Interleukin, Fibroblasts, Staphylococcal Infections, biochemical phenomena, metabolism, and nutrition, Pedigree, Protein Structure, Tertiary, Phosphotransferases (Alcohol Group Acceptor), Interleukin-1 Receptor-Associated Kinases, Mutation, Codon, Terminator, Cytokines, Female, Signal Transduction
Abstract

Members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily share an intracytoplasmic Toll–IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor–associated kinase (IRAK) complex via TIR-containing adapter molecules. We describe three unrelated children with inherited IRAK-4 deficiency. Their blood and fibroblast cells did not activate nuclear factor κB and mitogen-activated protein kinase (MAPK) and failed to induce downstream cytokines in response to any of the known ligands of TIR-bearing receptors. The otherwise healthy children developed infections caused by pyogenic bacteria. These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms.

Published
2003
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13. Acceptance of childhood and adolescent vaccination against COVID-19 in France: a national cross-sectional study in May 2021

Author

Pierre Verger, Patrick Peretti-Watel, Amandine Gagneux-Brunon, Elisabeth Botelho-Nevers, Alvaro Sanchez, Fatima Gauna, Lisa Fressard, Marion Bonneton, Odile Launay, and Jeremy K. Ward

Subjects
covid-19 vaccination, children and adolescents, vaccine acceptance, vaccines perception, vaccination campaign, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

The French health authorities extended vaccination against COVID-19 to adolescents in June 2021, during the epidemic resurgence linked to the delta variant and because of insufficient vaccination coverage to ensure collective protection. In May 2021, we conducted a national online cross-sectional survey of 2533 adults in France to study their attitudes toward COVID-19 vaccines and their acceptance of child/adolescent vaccination according to targeted age groups (

Published
2021
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14. Bacterial vaginosis and other infections in pregnant women in Senegal

Author

Marion Bonneton, Bich-Tram Huynh, Abdoulaye Seck, Raymond Bercion, Fatoumata Diene Sarr, Elisabeth Delarocque-Astagneau, and Muriel Vray

Subjects
Bacterial vaginosis, Vaginal microbiome, Pregnant women, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Bacterial vaginosis (BV) is associated with a higher risk of preterm delivery and spontaneous abortion. Yet little data on BV prevalence exist for sub-Saharan countries. The aim of this study was to estimate the prevalence of bacterial vaginosis and associated risk factors among pregnant women in Senegal. Methods From October 2013 to December 2018, pregnant women in their third trimester were recruited in two primary health centers (one suburban, one rural) in Senegal. Healthcare workers interviewed women and collected a lower vaginal swab and a blood sample. Vaginal flora were classified into four categories using vaginal smear microscopic examination and Gram’s coloration. In our study, BV was defined as vaginal flora with no Lactobacillus spp. Variables associated with BV were analyzed using STATA® through univariate and multivariate analysis. Results A total of 457 women provided a vaginal sample for analysis. Overall, BV prevalence was 18.6% (85/457) [95% CI 15.4–22.6]) and was similar in suburban and rural areas (18.9% versus 18.1%, p = 0.843). Multivariate analysis showed that primigravidity was the only factor independently associated with a lower risk of BV (aOR 0.35 [95% CI 0.17–0.72]). Conclusions Our study showed significant BV prevalence among pregnant women in Senegal. Although the literature has underscored the potential consequences of BV for obstetric outcomes, data are scarce on BV prevalence in sub-Saharan African countries. Before authorities consider systematic BV screening for pregnant women, a larger study would be useful in documenting prevalence, risk factors and the impact of BV on pregnancy outcomes.

Published
2021
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15. [CYLD deubiquitinase as a recurrent target in oncogenic processes]

Author

Marion, Bonnet and Gilles, Courtois

Subjects
Skin Neoplasms, Tumor Suppressor Proteins, NF-kappa B, Ubiquitination, Models, Biological, Deubiquitinating Enzyme CYLD, Neoplasm Proteins, Cell Transformation, Neoplastic, Gene Expression Regulation, Neoplastic Syndromes, Hereditary, Neoplasms, Humans, Genes, Tumor Suppressor, Protein Processing, Post-Translational, Signal Transduction
Abstract

CYLD deubiquitinase has been originally defined as a tumor suppressor based exclusively on genetic findings. Indeed, inactivation of CYLD in humans results in familial cylindromatosis and multiple trichoepithelioma, two pathologies characterized by the development of tumors originating specifically from the skin appendages. A set of recent publications has revealed that recurrent inactivation of CYLD occurs through diverse mechanisms in several forms of cancer, unequivocally confirming its tumor suppressor function. This property is associated with the critical role played by CYLD in negatively regulating several signaling pathway, among them the NF-κB signaling pathway.

Published
2011

16. Intention to participate in COVID-19 vaccine clinical trials in May 2021: a cross-sectional survey in the general French population

Author

Amandine Gagneux-Brunon, Jeremy K. Ward, Marion Bonneton, Pierre Verger, Odile Launay, and Elisabeth Botelho-Nevers

Subjects
vaccine, covid-19, trial, participation, attitudes, clinical research, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

In May 2021, while the immunization campaign was in progress, the emergence of new SARS-CoV-2 variants led us to assess attitudes toward participation in a COVID-19 vaccine clinical trial (VCT) in France. Between the 10th and the 23rd of May 2021, we conducted a cross-sectional online survey among a representative sample of the French population aged 18 and over and a specific sample of the French population over 65. Among the 3,056 respondents, 28.0% (856) would consider participation in a COVID-19 VCT. Factors independently negatively associated with willingness to participate in a COVID-19 VCT were female gender with an adjusted odd ratio (aOR) 0.42 and 95% confidence interval (95% CI) 0.35–0.51, and mistrust in health actors (in their own physician and pharmacists, health ministry, government, scientists in medias, medias and pharmaceutical companies) with aOR 0.86 (95% CI 0.84–0.88) by one-point increase in mistrust in health actors score. Factors positively associated with willingness to participate in a COVID-19 VCT were COVID-19 vaccination or intention to get vaccinated with aOR 4.89 (95% CI 3.15–7.61), being a healthcare worker with aOR 2.051 (95% CI 1.51–2.80), being at risk for severe COVID-19 with aOR 1.39 (95% CI 1.14–1.69) and altruism as the main reason for getting vaccination with aOR 1.56 (95% CI 1.29–1.88). In May 2021, despite COVID 19 vaccine availability, 28% of the French population would agree to participate in a COVID-19 VCT. Mistrust in health actors contributes to a reduction in the intention to participate. Attitudes toward COVID-19 vaccination predict attitudes toward participation in a COVID-19 VCT.

Published
2022
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17. A national platform for Covid-19 vaccine studies recruitment in France: Covireivac volunteer’s characteristics

Author

Marion Bonneton, Jessica Sambourg, Liem Binh Luong Nguyen, Christine Trillou, Joyce Dohou, Olivier Saint Lary, Mathieu Schuers, Marie Lachâtre, and Odile Launay

Subjects
vaccine, covid-19, patient selection, clinical trial, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

During the Covid-19 pandemic, the urgent need for safe and effective vaccines has led to many vaccine trials, implying fast and extensive recruitment of volunteers. In France, until 2020, vaccine clinical research participants were usually recruited locally, through center-based pools of volunteers, and local communication plans. Covireivac is a French public online platform launched on 10/01/2020 that enables national, large-scale recruitment of volunteers for Covid-19 vaccine studies. On the Covireivac website, all adult participants registered online, gave their informed consent, and filled out two online forms with information on their identity, health status (comorbidities, treatments), and known exposure to SARS-CoV-2. Since July 2021, volunteers could mention if their children are interested in participating in a Covid-19 vaccine trial. The objective of this work is to describe Covireivac’s volunteer characteristics registered from 10/01/2020 to 11/02/2022. To identify independent volunteer characteristics associated with a period of registration we performed a multivariate logistic regression. Among 54,424 registrations, 52,391 (96%) were analysed; 61% were male (n = 31,893), median age was 50 y; 13% (n = 6586) were healthcare workers. At registration, 15,879 volunteers (33%) reported at least one comorbidity, among whom 16% (n = 7349) were obese and 17% (n = 8346) had hypertension. Most volunteers registered during the first month (n = 35,876, 66%). The Covireivac platform allowed quick and large recruitment of potential volunteers for Covid-19 vaccine trials and could be used on a larger scale for vaccine trials in France. It could facilitate recruitment in vaccine trials and provide sponsors with better visibility of the recruitment capacities of clinical research centers.

Published
2022
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18. In vivo evidence for quasispecies distributions in the bovine respiratory syncytial virus genome

Author

Gilles Meyer, François Schelcher, Mylène Lemaire, Carole Mirandette, Martine Deplanche, Marion Bonnet, Institut National de la Recherche Agronomique - INRA (FRANCE), Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Inconnu, and ProdInra, Migration

Subjects
Paramyxoviridae, 040301 veterinary sciences, Evolution, [SDV]Life Sciences [q-bio], Mutant, Population, Cattle Diseases, Respiratory Syncytial Virus, Bovine, Viral quasispecies, Genome, Viral, Respiratory Syncytial Virus Infections, medicine.disease_cause, BRSV, Virus, 0403 veterinary science, 03 medical and health sciences, Viral Envelope Proteins, Virology, medicine, Animals, Amino Acid Sequence, Variability, Mononegavirales, education, Antigens, Viral, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, 0303 health sciences, education.field_of_study, Mutation, Polymorphism, Genetic, biology, Sequence Homology, Amino Acid, Genetic heterogeneity, 04 agricultural and veterinary sciences, Sequence Analysis, DNA, biology.organism_classification, 3. Good health, Protein Structure, Tertiary, [SDV] Life Sciences [q-bio], Quasispecies, Médecine vétérinaire et santé animal, Cattle
Abstract

We analysed the genetic evolution of bovine respiratory syncytial virus (BRSV) isolate W2-00131, from its isolation in bovine turbinate (BT) cells to its inoculation in calves. Results showed that the BRSV genomic region encoding the highly variable glycoprotein G remained genetically stable after virus isolation and over 10 serial infections in BT cells, as well as following experimental inoculation in calves. This remarkable genetic stability led us to examine the mutant spectrum of several populations derived from this field isolate. Sequence analysis of molecular clones revealed an important genetic heterogeneity in the G-coding region of each population, with mutation frequencies ranging from 6.8 to 10.1×10−4substitutions per nucleotide. The non-synonymous mutations of the mutant spectrum mapped preferentially within the two variable antigenic regions of the ectodomain or close to the highly conserved domain. These results suggest that BRSV populations may evolve as complex and dynamic mutant swarms, despite apparent genetic stability.

Published
2007

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