Publications by authors named "Francois Spertini"

111 Publications

Designs and Characterization of Subunit Ebola GP Vaccine Candidates: Implications for Immunogenicity.

Front Immunol 2020 4;11:586595. Epub 2020 Nov 4.

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

The humoral responses of Ebola virus (EBOV) survivors mainly target the surface glycoprotein GP, and anti-GP neutralizing antibodies have been associated with protection against EBOV infection. In order to elicit protective neutralizing antibodies through vaccination a native-like conformation of the antigen is required. We therefore engineered and expressed in CHO cells several GP variants from EBOV (species , Mayinga variant), including a soluble GP ΔTM, a mucin-like domain-deleted GP ΔTM-ΔMUC, as well as two GP ΔTM-ΔMUC variants with C-terminal trimerization motifs in order to favor their native trimeric conformation. Inclusion of the trimerization motifs resulted in proteins mimicking GP metastable trimer and showing increased stability. The mucin-like domain appeared not to be critical for the retention of the native conformation of the GP protein, and its removal unmasked several neutralizing epitopes, especially in the trimers. The soluble GP variants inhibited mAbs neutralizing activity in a pseudotype transduction assay, further confirming the proteins' structural integrity. Interestingly, the trimeric GPs, a native-like GP complex, showed stronger affinity for antibodies raised by natural infection in EBOV disease survivors rather than for antibodies raised in volunteers that received the ChAd3-EBOZ vaccine. These results support our hypothesis that neutralizing antibodies are preferentially induced when using a native-like conformation of the GP antigen. The soluble trimeric recombinant GP proteins we developed represent a novel and promising strategy to develop prophylactic vaccines against EBOV and other filoviruses.
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http://dx.doi.org/10.3389/fimmu.2020.586595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672190PMC
November 2020

and Orthologous Coiled-Coil Candidates for a Potential Cross-Protective Vaccine.

Front Immunol 2020 21;11:574330. Epub 2020 Oct 21.

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

Over the last four decades, significant efforts have been invested to develop vaccines against malaria. Although most efforts are focused on the development of vaccines, the current availability of the parasite genomes, bioinformatics tools, and high throughput systems for both recombinant and synthetic antigen production have helped to accelerate vaccine development against the parasite. We have previously identified several and proteins containing α-helical coiled-coil motifs that represent novel putative antigens for vaccine development since they are highly immunogenic and have been associated with protection in many functional assays. Here, we selected five pairs of and orthologous peptides to assess their sero-reactivity using plasma samples collected in endemic African countries. cross-reactivity was also investigated. The pairs , and resulted to be the most promising candidates for a cross-protective vaccine because they showed a high degree of recognition in direct and competition ELISA assays and cross-reactivity with their respective ortholog. The recognition of peptides by plasma of infected individuals indicates the existence of a high degree of cross-reactivity between these two species. The design of longer polypeptides combining these epitopes will allow the assessment of their immunogenicity and protective efficacy in animal models.
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http://dx.doi.org/10.3389/fimmu.2020.574330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609509PMC
October 2020

Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI), Österreichische Gesellschaft für Pneumologie (ÖGP) in co-operation with the German, Austrian, and Swiss ARIA groups, and the European Academy of Allergy and Clinical Immunology (EAACI).

Authors:
Ludger Klimek Oliver Pfaar Margitta Worm Thomas Eiwegger Jan Hagemann Markus Ollert Eva Untersmayr Karin Hoffmann-Sommergruber Alessandra Vultaggio Ioana Agache Sevim Bavbek Apostolos Bossios Ingrid Casper Susan Chan Alexia Chatzipetrou Christian Vogelberg Davide Firinu Paula Kauppi Antonios Kolios Akash Kothari Andrea Matucci Oscar Palomares Zsolt Szépfalusi Wolfgang Pohl Wolfram Hötzenecker Alexander R Rosenkranz Karl-Christian Bergmann Thomas Bieber Roland Buhl Jeroen Buters Ulf Darsow Thomas Keil Jörg Kleine-Tebbe Susanne Lau Marcus Maurer Hans Merk Ralph Mösges Joachim Saloga Petra Staubach Uta Jappe Klaus F Rabe Uta Rabe Claus Vogelmeier Tilo Biedermann Kirsten Jung Wolfgang Schlenter Johannes Ring Adam Chaker Wolfgang Wehrmann Sven Becker Laura Freudelsperger Norbert Mülleneisen Katja Nemat Wolfgang Czech Holger Wrede Randolf Brehler Thomas Fuchs Peter-Valentin Tomazic Werner Aberer Antje-Henriette Fink-Wagner Fritz Horak Stefan Wöhrl Verena Niederberger-Leppin Isabella Pali-Schöll Wolfgang Pohl Regina Roller-Wirnsberger Otto Spranger Rudolf Valenta Mübecell Akdis Paolo M Matricardi François Spertini Nicolai Khaltaev Jean-Pierre Michel Larent Nicod Peter Schmid-Grendelmeier Marco Idzko Eckard Hamelmann Thilo Jakob Thomas Werfel Martin Wagenmann Christian Taube Erika Jensen-Jarolim Stephanie Korn Francois Hentges Jürgen Schwarze Liam O Mahony Edward F Knol Stefano Del Giacco Tomás Chivato Pérez Jean Bousquet Anna Bedbrook Torsten Zuberbier Cezmi Akdis Marek Jutel

Allergol Select 2020 7;4:53-68. Epub 2020 Sep 7.

European Academy of Allergy and Clinical Immunology (EAACI).

Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.

Materials And Methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.

Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.

Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.
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http://dx.doi.org/10.5414/ALX02166EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480069PMC
September 2020

Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemie: Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H.

Allergo J 2020 24;29(4):14-27. Epub 2020 Jun 24.

Zentrum für Rhinologie & Allergologie, An den Quellen 10, 65183 Wiesbaden, Germany.

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http://dx.doi.org/10.1007/s15007-020-2553-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289636PMC
June 2020

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Authors:
Jean Bousquet Josep M Anto Claus Bachert Tari Haahtela Torsten Zuberbier Wienczyslawa Czarlewski Anna Bedbrook Sinthia Bosnic-Anticevich G Walter Canonica Victoria Cardona Elisio Costa Alvaro A Cruz Marina Erhola Wytske J Fokkens Joao A Fonseca Maddalena Illario Juan-Carlos Ivancevich Marek Jutel Ludger Klimek Piotr Kuna Violeta Kvedariene Ltt Le Désirée E Larenas-Linnemann Daniel Laune Olga M Lourenço Erik Melén Joaquim Mullol Marek Niedoszytko Mikaëla Odemyr Yoshitaka Okamoto Nikos G Papadopoulos Vincenzo Patella Oliver Pfaar Nhân Pham-Thi Christine Rolland Boleslaw Samolinski Aziz Sheikh Mikhail Sofiev Charlotte Suppli Ulrik Ana Todo-Bom Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Samantha Walker Sian Williams Arzu Yorgancioglu Ioana Agache Cezmi A Akdis Rute Almeida Ignacio J Ansotegui Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagaña Eric D Bateman Annabelle Bédard Martin Bedolla-Barajas Sven Becker Kazi S Bennoor Samuel Benveniste Karl C Bergmann Michael Bewick Slawomir Bialek Nils E Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Matteo Bonini Philippe Bonniaud Isabelle Bosse Jacques Bouchard Louis-Philippe Boulet Rodolphe Bourret Koen Boussery Fluvio Braido Vitalis Briedis Andrew Briggs Christopher E Brightling Jan Brozek Guy Brusselle Luisa Brussino Roland Buhl Roland Buonaiuto Moises A Calderon Paulo Camargos Thierry Camuzat Luis Caraballo Ana-Maria Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Niels H Chavannes Ekaterine Chkhartishvili Derek K Chu Cemal Cingi Jaime Correia de Sousa David J Costa Anne-Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejan Dokic Yves Dauvilliers Giulia De Feo Govert De Vries Philippe Devillier Stefania Di Capua Gerard Dray Ruta Dubakiene Stephen R Durham Mark Dykewicz Motohiro Ebisawa Mina Gaga Yehia El-Gamal Enrico Heffler Regina Emuzyte John Farrell Jean-Luc Fauquert Alessandro Fiocchi Antje Fink-Wagner Jean-François Fontaine José M Fuentes Perez Bilun Gemicioğlu Amiran Gamkrelidze Judith Garcia-Aymerich Philippe Gevaert René Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam Yunuen R Huerta Villalobos Marc Humbert Guido Iaccarino Despo Ierodiakonou Tomohisa Iinuma Ewa Jassem Guy Joos Ki-Suck Jung Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Musa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Rostislav Kouznetsov Marek L Kowalski Vicky Kritikos Inger Kull Stefania La Grutta Lisa Leonardini Henrik Ljungberg Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Catarina Lopes-Pereira Claudia C Loureiro Renaud Louis Alpana Mair Bassam Mahboub Michaël Makris Joao Malva Patrick Manning Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Pedro Carreiro-Martins Mika Makela Eve Mathieu-Dupas Marcus Maurer Esteban De Manuel Keenoy Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Yann Micheli Neven Miculinic Florin Mihaltan Branislava Milenkovic Dimitirios I Mitsias Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralph Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leyla Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Björn Nordlund Ettore Novellino Dieudonné Nyembue Robyn O'Hehir Ken Ohta Kimi Okubo Gabrielle L Onorato Valentina Orlando Solange Ouedraogo Julia Palamarchuk Isabella Pali-Schöll Peter Panzner Hae-Sim Park Gianni Passalacqua Jean-Louis Pépin Ema Paulino Ruby Pawankar Jim Phillips Robert Picard Hilary Pinnock Davor Plavec Todor A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Fotis Psarros Benoit Pugin Francesca Puggioni Pablo Quinones-Delgado Filip Raciborski Rojin Rajabian-Söderlund Frederico S Regateiro Sietze Reitsma Daniela Rivero-Yeverino Graham Roberts Nicolas Roche Erendira Rodriguez-Zagal Christine Rolland Regina E Roller-Wirnsberger Nelson Rosario Antonino Romano Menachem Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Joaquin Sastre Glenis K Scadding Sophie Scheire Peter Schmid-Grendelmeier Holger J Schünemann Faradiba Sarquis Serpa Mohamed Shamji Juan-Carlos Sisul Mikhail Sofiev Dirceu Solé David Somekh Talant Sooronbaev Milan Sova François Spertini Otto Spranger Cristiana Stellato Rafael Stelmach Michel Thibaudon Teresa To Mondher Toumi Omar Usmani Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Marilyn Urrutia Pereira Rianne van der Kleij Michiel Van Eerd Olivier Vandenplas Tuula Vasankari Antonio Vaz Carneiro Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Yun Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Osman M Yusuf Heather J Zar Stéphane Zeng Mario E Zernotti Luo Zhang Nan Shan Zhong Mihaela Zidarn

Allergy 2021 01 23;76(1):168-190. Epub 2020 Oct 23.

University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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http://dx.doi.org/10.1111/all.14422DOI Listing
January 2021

Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy.

Oncoimmunology 2020 21;9(1):1748981. Epub 2020 Apr 21.

Department of Oncology, University Hospital Basel, University of Basel, Switzerland.

: VPM1002BC is a modified mycobacterium Bacillus Calmette Guérin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC). The genetic modifications are expected to result in better immunogenicity and less side effects. We report on patient safety and immunology of the first intravesical application of VPM1002BC in human. : Six patients with BCG failure received a treatment of 6 weekly instillations with VPM1002BC. Patients were monitored for adverse events (AE), excretion of VPM1002BC and cytokines, respectively. : No DLT (dose limiting toxicity) occurred during the DLT-period. No grade ≥3 AEs occurred. Excretion of VPM1002BC in the urine was limited to less than 24 hours. Plasma levels of TNFα significantly increased after treatment and blood-derived CD4+ T cells stimulated with PPD demonstrated significantly increased intracellular GM-CSF and IFN expression. : The intravesical application of VPM1002BC is safe and well tolerated by patients and results in a potential Th1 weighted immune response.
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http://dx.doi.org/10.1080/2162402X.2020.1748981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185202PMC
April 2020

[Allergy to furry animals: myth and reality].

Rev Med Suisse 2020 Apr;16(689):688-693

Service d'immunologie et allergie, Département de médecine, CHUV, 1011 Lausanne.

Allergy to furry animals is a frequent health issue, and should be suspected when investigating any yearlong rhinoconjonctivitis or asthma. A detailed medical history and skin prick tests are usually sufficient for diagnosis, and if necessary, specific IgE testing may be performed. In case of proven hypersensitivity, avoidance of animal allergens is the main therapeutic measure, primarily by removing the animal from the patient's environment, in association with symptomatic treatment. If animal removing is impossible, other measures exist to decrease allergen load, but not with the same -efficacy as removing the animal, particularly for asthma. Immunotherapy is available for cat and dog allergy, but indication is to be carefully discussed.
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April 2020

Jamais sans mon chat !

Rev Med Suisse 2020 Apr;16(689):667-668

Service d'immunologie et d'allergologie, HUG, Genève.

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April 2020

Epitope Mapping and Fine Specificity of Human T and B Cell Responses for Novel Candidate Blood-Stage Malaria Vaccine P27A.

Front Immunol 2020 10;11:412. Epub 2020 Mar 10.

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

P27A is a novel synthetic malaria vaccine candidate derived from the blood stage protein Trophozoite Exported Protein 1 (TEX1/PFF0165c). In phase 1a/1b clinical trials in malaria unexposed adults in Switzerland and in malaria pre-exposed adults in Tanzania, P27A formulated with Alhydrogel and GLA-SE adjuvants induced antigen-specific antibodies and T-cell activity. The GLA-SE adjuvant induced significantly stronger humoral responses than the Alhydrogel adjuvant. Groups of pre-exposed and unexposed subjects received identical vaccine formulations, which supported the comparison of the cellular and humoral response to P27A in terms of fine specificity and affinity for populations and adjuvants. Globally, fine specificity of the T and B cell responses exhibited preferred recognized sequences and did not highlight major differences between adjuvants or populations. Affinity of anti-P27A antibodies was around 10 M in all groups. Pre-exposed volunteers presented anti-P27A with higher affinity than unexposed volunteers. Increasing the dose of GLA-SE from 2.5 to 5 μg in pre-exposed volunteers improved anti-P27A affinity and decreased the number of recognized epitopes. These results indicate a higher maturation of the humoral response in pre-exposed volunteers, particularly when immunized with P27A formulated with 5 μg GLA-SE.
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http://dx.doi.org/10.3389/fimmu.2020.00412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076177PMC
March 2020

Metabolomics and allergy: Opening Pandora's box.

J Allergy Clin Immunol 2020 03 22;145(3):782-784. Epub 2020 Jan 22.

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2020.01.012DOI Listing
March 2020

Management of allergy transfer upon solid organ transplantation.

Am J Transplant 2020 03 19;20(3):834-843. Epub 2019 Oct 19.

Division of Immunology and Allergy, Department of Medicine, University Hospitals and University of Geneva, Geneva, Switzerland.

Allergy transfer upon solid organ transplantation has been reported in the literature, although only few data are available as to the frequency, significance, and management of these cases. Based on a review of 577 consecutive deceased donors from the Swisstransplant Donor-Registry, 3 cases (0.5%) of fatal anaphylaxis were identified, 2 because of peanut and 1 of wasp allergy. The sera of all 3 donors and their 10 paired recipients, prospectively collected before and after transplantation for the Swiss Transplant Cohort Study, were retrospectively processed using a commercial protein microarray fluorescent test. As early as 5 days posttransplantation, newly acquired peanut-specific IgE were transiently detected from 1 donor to 3 recipients, of whom 1 liver and lung recipients developed grade III anaphylaxis. Yet, to define how allergy testing should be performed in transplant recipients and to better understand the impact of immunosuppressive therapy on IgE sensitization, we prospectively studied 5 atopic living-donor kidney recipients. All pollen-specific IgE and >90% of skin prick tests remained positive 7 days and 3 months after transplantation, indicating that early diagnosis of donor-derived IgE sensitization is possible. Importantly, we propose recommendations with respect to safety for recipients undergoing solid-organ transplantation from donors with a history of fatal anaphylaxis.
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http://dx.doi.org/10.1111/ajt.15601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065229PMC
March 2020

Novel Nanofluidic IgE Assay versus a Reference Method: A Real-World Comparison.

Int Arch Allergy Immunol 2019 12;180(1):28-36. Epub 2019 Jun 12.

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Background: Clinically meaningful specific IgE determination is an important step in the diagnosis of allergic diseases. While patient's history and skin prick tests are available during the medical visit, most IgE immunoassays require hours to several days to be available. Recent developments in the field of nanofluidic technology open new horizons for point-of-care management of this unmet medical need.

Objective: This study aimed to compare IgE diagnostic agreement between a nanofluidic assay (abioSCOPE®) and a laboratory reference method (Phadia Laboratory System®) in a real-world clinical setting.

Methods: Sera from 105 patients whose routine allergy diagnostic workup required a blood sampling were used to compare the novel nanofluidic IgE assay to a reference method in a blind manner for a panel of five respiratory allergens. To assess the agreement between methods, patient records were reviewed by four independent experts to establish the final diagnosis. Experts were blinded to the IgE serological method used, but had access to patient history, skin prick tests, and blood test results.

Results: Analytic agreement between the two methods was 81% for the tested panel of allergens (ranging from 77 to 89%). The overall agreement in clinical diagnosis decision taken by the expert panel was 94.6% with the nanofluidic IgE assay when compared to the reference method.

Conclusion: The nanofluidic IgE assay, as determined through an evaluation based on clinical history, skin prick tests, and IgE measurement, is a valuable tool for allergy experts to identify patients' sensitization patterns at the point of care, and for routine IgE diagnostic workup.
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http://dx.doi.org/10.1159/000500830DOI Listing
September 2019

The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes.

J Exp Med 2019 08 7;216(8):1857-1873. Epub 2019 Jun 7.

Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, UK

The generation of protective humoral immunity after vaccination relies on the productive interaction between antigen-specific B cells and T follicular helper (Tfh) cells. Despite the central role of Tfh cells in vaccine responses, there is currently no validated way to enhance their differentiation in humans. From paired human lymph node and blood samples, we identify a population of circulating Tfh cells that are transcriptionally and clonally similar to germinal center Tfh cells. In a clinical trial of vaccine formulations, circulating Tfh cells were expanded in Tanzanian volunteers when an experimental malaria vaccine was adjuvanted in GLA-SE but not when formulated in Alum. The GLA-SE-formulated peptide was associated with an increase in the extrafollicular antibody response, long-lived antibody production, and the emergence of public TCRβ clonotypes in circulating Tfh cells. We demonstrate that altering vaccine adjuvants is a rational approach for enhancing Tfh cells in humans, thereby supporting the long-lived humoral immunity that is required for effective vaccines.
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http://dx.doi.org/10.1084/jem.20190301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683991PMC
August 2019

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.

Nat Rev Clin Oncol 2019 09;16(9):563-580

Service Immunologie et Allergie, CHUV, Lausanne, Switzerland.

Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.
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http://dx.doi.org/10.1038/s41571-019-0218-0DOI Listing
September 2019

Davantage de silence.

Rev Med Suisse 2019 04;15(645):703-704

Service d'immunologie et allergie, CHUV, Lausanne.

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April 2019

[Risk of treatment failure and therapeutic novelties in asthma].

Rev Med Suisse 2019 Jan;15(N° 632-633):23-26

Service d'immunologie et allergie, Département de médecine interne, CHUV, 1001 Lausanne.

Asthma is a chronic disease that is still frequently poorly controlled, despite recent advances in understanding its pathophysiology. Poor compliance and ineffective inhalation technique remain the main causes of treatment failure. The comorbidities associated with asthma, such as obesity and chronic rhinosinusitis, are other elements to consider in the management of patients. Biological treatments targeting inflammation mediators show encouraging results in recurrent asthma exacerbations despite optimal management. However, their benefit remains limited to certain patients, thus requiring the study of predictive biomarkers to better delineate their indication.
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January 2019

[Where are we with oral immunotherapy for food allergy ?]

Rev Med Suisse 2019 Jan;15(N° 632-633):20-22

Service d'immunologie et allergie, CHUV, 1011 Lausanne.

In allergology, food allergy is probably the problem to which medicine has brought the least therapeutic response so far. While oral immunotherapy for peanut, egg and milk is reserved for a few special cases and is not routinely recommended, apple desensitization for adult oral syndrome seems to bring some benefits in clinical practice, particularly in patients with restricted diet in fruits.
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January 2019

New therapeutic perspectives to manage refractory immune checkpoint-related toxicities.

Lancet Oncol 2019 01;20(1):e54-e64

Service Immunologie et Allergie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Centre d'Immunothérapie et de Vaccinologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Faculté Médecine Paris Descartes, Université Paris Descartes, Paris, France. Electronic address:

Immune checkpoint inhibitors are reshaping the prognosis of many cancer and are progressively becoming the standard of care in the treatment of many tumour types. Immunotherapy is bringing new hope to patients, but also a whole new spectrum of toxicities for healthcare practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of patients with cancer are increasingly confronted with the therapeutic challenge of treating patients with severe and refractory immune-related adverse events. In this Personal View, we summarise the therapeutic strategies that have been used to manage such toxicities resulting from immune checkpoint inhibitor treatment. On the basis of current knowledge about their pathogenesis, we discuss the use of new biological and non-biological immunosuppressive drugs to treat severe and steroid refractory immune-related adverse events. Depending on the immune infiltrate type that is predominant, we propose a treatment algorithm for personalised management that goes beyond typical corticosteroid use. We propose a so-called shut-off strategy that aims at inhibiting key inflammatory components involved in the pathophysiological processes of immune-related adverse events, and limits potential adverse effects of drug immunosuppression on tumour response. This approach develops on current guidelines and challenges the step-by-step increase approach to drug immunosuppression.
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http://dx.doi.org/10.1016/S1470-2045(18)30828-3DOI Listing
January 2019

A severe case of refractory esophageal stenosis induced by nivolumab and responding to tocilizumab therapy.

J Immunother Cancer 2018 12 27;6(1):156. Epub 2018 Dec 27.

Department of Medicine, Division of Immunology and Allergy, Lausanne University Hospital CHUV, rue du Bugnon 46, CH-1011, Lausanne, Switzerland.

Background: The prevalence of esophageal stenosis caused by immune checkpoint inhibitors in the context of induced immune mucositis and esophagitis is extremely rare.

Case Presentation: We report the case of a patient with stage IV pulmonary adenocarcinoma treated for 6 months with nivolumab who developed bilateral sterile conjunctivitis followed by oropharyngeal mucositis and esophagitis complicated by a severe esophageal stenosis. The laryngeal margin and hypopharyngeal mucosa appeared highly inflammatory with fibrinous deposits. Esophagogastroduodenoscopy revealed mucositis with a scar-like structure immediately below the upper esophageal sphincter with nonulcerative mucosa and an inflammatory aspect of the entire esophagus. No involvement of the stomach was observed. Oropharynx biopsies displayed marked lymphocytic T cell-infiltration with several foci of monocellular necrosis in the squamous epithelium. No morphologic evidence of adenocarcinoma and no signs of mycotic, bacterial or viral infection were noted. A blood sample revealed a discrete increase in the erythrocyte sedimentation rate (ESR) with no eosinophilia or leukocytosis. Liver and kidney function panel tests were normal. A thoracoabdominal CT scan reported no evidence of disease recurrence. Despite multiple boluses of methylprednisolone and high doses of prednisone continued for several months, the patient experienced very rapid symptomatological reappearance during three steroid tapering attempts and aggravation of his esophageal stenosis to an aphagic stage, requiring a nasogastric tube. This long course of high-dose corticosteroid treatment was complicated with osteoporosis-induced fractures with several spontaneous compressions of thoracolumbar vertebrae requiring an enlarged T10 to L5 cementoplasty. Anti-IL-6 blockade therapy with tocilizumab resulted in excellent clinical response, allowing the total resolution of the immune-related adverse events (irAEs) and leading to successful steroid tapering.

Conclusions: Herein, we describe the first case of a patient who developed autoimmune mucositis and esophagitis complicated by a severe refractory esophageal stenosis induced during treatment by nivolumab, which completely resolved after personalized treatment with tocilizumab, suggesting a role of IL-6 blockade in the management of severe steroid refractory esophageal stenosis and more broadly in refractory immune-related adverse events.
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http://dx.doi.org/10.1186/s40425-018-0481-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307169PMC
December 2018

Supplemental parenteral nutrition improves immunity with unchanged carbohydrate and protein metabolism in critically ill patients: The SPN2 randomized tracer study.

Clin Nutr 2019 10 5;38(5):2408-2416. Epub 2018 Nov 5.

Clinical Nutrition, Geneva University Hospital, 1205 Geneva, Switzerland.

Background & Aims: Individualized supplemental parenteral nutrition (SPN) providing measured energy expenditure from day 4 reduced infectious complications in a previous study including 305 intensive care (ICU) patients. The study aimed at investigating the metabolic, and immune responses underlying the clinical response of the previous trial.

Methods: Randomized controlled trial enrolling 23 critically ill patients on day 3 (D3) of admission to the ICU who were fed less than 60% of their energy target by the enteral nutrition (EN) alone: allocation to either continued EN or to SPN to a target validated by indirect calorimetry. Protein and glucose metabolism (primary endpoint) were investigated with tracer isotopes on D4 and D9. Secondary endpoints: 1) immune response, investigated in serum and in stimulated peripheral blood mononuclear cells (PMBC), by dosing a panel of cytokines (infectious complications were recorded), and 2) Muscle mass was assessed by ultrasound of the thigh.

Results: Comparable at baseline, the SPN group (n = 11) received more energy (median 24.3 versus 17.8 kcal/kg/day: p < 0.001) and proteins (1.11 versus 0.69 g/kg/day: p < 0.001) than the control group during the five days' intervention, resulting in a less negative energy balance by D9 (p = 0.0027). Net protein breakdown and Glucose kinetics on D9 did not differ, within or between groups. In agreement with a decrease in infection rate, immune response in the SPN group showed decreased serum IL-6 (p = 0.024), IL-1β, IL-10 levels and TNF-α secretion by PBMC (p = 0.018) at D9. Muscle mass loss from D4 to D15 tended to be less in the SPN group (-16% versus -23%: p = 0.06). Clinical course by D28 did not differ.

Conclusions: Feeding patients to cover an individualised measured energy target with SPN from D4 to cover needs, was associated with improved immunity, less systemic inflammation and a trend to less muscle mass loss.

Clinical Trial Registry: NCT02022813 at https://clinicaltrials.gov/.
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http://dx.doi.org/10.1016/j.clnu.2018.10.023DOI Listing
October 2019

Prospective evaluation of the capillaroscopic skin ulcer risk index in systemic sclerosis patients in clinical practice: a longitudinal, multicentre study.

Arthritis Res Ther 2018 Oct 25;20(1):239. Epub 2018 Oct 25.

Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.

Background: Nailfold capillaroscopy (NC) is an important tool for the diagnosis of systemic sclerosis (SSc). The capillaroscopic skin ulcer risk index (CSURI) was suggested to identify patients at risk of developing digital ulcers (DUs). This study aims to assess the reliability of the CSURI across assessors, the CSURI change during follow-up and the value of the CSURI in predicting new DUs.

Methods: This multicentre, longitudinal study included SSc patients with a history of DUs. NC images of all eight fingers were obtained at baseline and follow-up and were separately analysed by two trained assessors.

Results: Sixty-one patients were included (median observation time 1.0 year). In about 40% of patients (assessor 1, n = 24, 39%; assessor 2, n = 26, 43%) no megacapillary was detected in any of the baseline or follow-up images; hence the CSURI could not be calculated. In those 34 patients in whom CSURI scores were available from both assessors (26% male; median age 57 years) the median baseline CSURI was 5.3 according to assessor 1 (IQR 2.6-16.3), increasing to 5.9 (IQR 1.3-12.0) at follow-up. According to assessor 2, the CSURI diminished from 6.4 (IQR 2.4-12.5) to 5.0 (IQR 1.7-10.0). The ability of a CSURI ≥ 2.96 category to predict new DUs was low (for both assessors, positive predictive value 38% and negative predictive value 50%) and the inter-assessor agreements for CSURI categories were fair to moderate.

Conclusions: In this study, around 40% of patients could not be evaluated with the CSURI due to the absence of megacapillaries. Clinical decisions based on the CSURI should be made with caution.

Trial Registration: Current Controlled Trials, ISRCTN04371709 . Registered on 18 March 2011.
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http://dx.doi.org/10.1186/s13075-018-1733-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235233PMC
October 2018

The Candidate Blood-stage Malaria Vaccine P27A Induces a Robust Humoral Response in a Fast Track to the Field Phase 1 Trial in Exposed and Nonexposed Volunteers.

Clin Infect Dis 2019 01;68(3):466-474

Ifakara Health Institute, Bagamoyo, Tanzania.

Background: P27A is an unstructured 104mer synthetic peptide from Plasmodium falciparum trophozoite exported protein 1 (TEX1), the target of human antibodies inhibiting parasite growth. The present project aimed at evaluating the safety and immunogenicity of P27A peptide vaccine in malaria-nonexposed European and malaria-exposed African adults.

Methods: This study was designed as a staggered, fast-track, randomized, antigen and adjuvant dose-finding, multicenter phase 1a/1b trial, conducted in Switzerland and Tanzania. P27A antigen (10 or 50 μg), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 μg), or control rabies vaccine (Verorab) were administered intramuscularly to 16 malaria-nonexposed and 40 malaria-exposed subjects on days 0, 28, and 56. Local and systemic adverse events (AEs) as well as humoral and cellular immune responses were assessed after each injection and during the 34-week follow-up.

Results: Most AEs were mild to moderate and resolved completely within 48 hours. Systemic AEs were more frequent in the formulation with alum as compared to GLA-SE, whereas local AEs were more frequent after GLA-SE. No serious AEs occurred. Supported by a mixed Th1/Th2 cell-mediated immunity, P27A induced a marked specific antibody response able to recognize TEX1 in infected erythrocytes and to inhibit parasite growth through an antibody-dependent cellular inhibition mechanism. Incidence of AEs and antibody responses were significantly lower in malaria-exposed Tanzanian subjects than in nonexposed European subjects.

Conclusions: The candidate vaccine P27A was safe and induced a particularly robust immunogenic response in combination with GLA-SE. This formulation should be considered for future efficacy trials.

Clinical Trials Registration: NCT01949909, PACTR201310000683408.
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http://dx.doi.org/10.1093/cid/ciy514DOI Listing
January 2019

Benefit of Bet v 1 contiguous overlapping peptide immunotherapy persists during first follow-up season.

J Allergy Clin Immunol 2018 08 17;142(2):678-680.e7. Epub 2018 Apr 17.

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2018.01.052DOI Listing
August 2018

[Sublingual immunotherapy for the treatment of allergic rhinoconjonctivitis and asthma : a practical approach].

Rev Med Suisse 2018 Apr;14(601):735-739

Service d'immunologie et allergologie, CHUV, 1011 Lausanne.

The prevalence of allergic diseases has been increasing over the past 50 years, leading to social and economic consequences. Immunotherapy is the only disease-modifying therapy available for allergic diseases, with durable long-term benefits. Immunotherapy is primarily available in two forms : 1) subcutaneous injections or 2) sublingual tablets/drops. The latter offers the advantage of being managed by the patient himself, requires no injections and has a far lower risk of severe systemic adverse events. In Switzerland, the use of sublingual immunotherapy is still scarce. This article reviews the indications, the administration technics and the contraindications to sublingual immunotherapy.
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April 2018

[Seasonal allergic rhinitis].

Rev Med Suisse 2018 Apr;14(601):726-730

Service d'immunologie et d'allergie, CHUV, 1011 Lausanne.

Allergic diseases are currently amongst the most frequent diseases of our time. Of all the allergies in the Western countries, allergic rhinoconjunctivitis is the most common. Its diagnosis is based mainly on the history and the correlation between symptoms and contact with the allergen. A step-by-step approach helps optimize diagnostic resources and minimize costs.
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April 2018

Nouvelles thérapeutiques et coûts de la médecine.

Rev Med Suisse 2018 Apr;14(601):723-724

Service d'immunologie et allergie, HUG, Genève.

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April 2018

Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease.

Ann Rheum Dis 2018 06 22;77(6):840-847. Epub 2018 Feb 22.

AB2 Bio Ltd, EPFL Innovation Park, Lausanne, Switzerland.

Objectives: Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option in AOSD.

Methods: In this phase II, open-label study, patients were ≥18 years with active AOSD plus fever or C reactive protein (CRP) levels ≥10 mg/L despite treatment with prednisone and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Previous biological DMARD treatment was permitted. Patients received tadekinig alfa 80 mg or 160 mg subcutaneously three times per week for 12 weeks; those receiving 80 mg not achieving early predicted response criteria (reduction of ≥50% CRP values from baseline and fever resolution) were up-titrated to 160 mg for a further 12 weeks. The primary endpoint was the occurrence of adverse events (AEs) throughout the study.

Results: Ten patients were assigned to receive 80 mg tadekinig alfa and 13 patients to the 160 mg dose. One hundred and fifty-five treatment-emerging AEs were recorded, and 47 were considered related to the study drug. Most AEs were mild and resolved after drug discontinuation. Three serious AEs occurred, one possibly related to treatment (toxic optic neuropathy). At week 3, 5 of 10 patients receiving 80 mg and 6 of 12 patients receiving 160 mg achieved the predefined response criteria.

Conclusions: Our results indicate that tadekinig alfa appears to have a favourable safety profile and is associated with early signs of efficacy in patients with AOSD.

Trial Registration Number: NCT02398435.
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http://dx.doi.org/10.1136/annrheumdis-2017-212608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965361PMC
June 2018

Sjögren's Disease Associated with Severe Retinal Vasculitis and/or Necrotizing Scleritis: Two Cases.

Klin Monbl Augenheilkd 2018 04 16;235(4):480-482. Epub 2018 Feb 16.

Ophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland.

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http://dx.doi.org/10.1055/s-0043-123641DOI Listing
April 2018

TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development.

Front Immunol 2017 4;8:1203. Epub 2017 Oct 4.

Public Health England, London, United Kingdom.

TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC). It aims at the discovery and development of novel tuberculosis (TB) vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, TBVAC2020 offers portfolio management that provides selection criteria for entry, gating, and priority settings of novel vaccines at an early developmental stage. The TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data sharing between partners with the common aim of working toward the development of an effective TB vaccine. Close links with funders and other consortia with shared interests further contribute to this goal.
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http://dx.doi.org/10.3389/fimmu.2017.01203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632681PMC
October 2017