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1. Characterization of enteroviruses circulating among farm animals and children in Central African Republic

Author

Joël Doté, Marie-Line Joffret, Bertille Ndombari Beta, Mohand Ait-Ahmed, Virginie Banga-Mingo, Nick J. Knowles, Nolwenn Jouvenet, Marie-Noël MBaïkoua, Ionela Gouandjika-Vasilache, and Maël Bessaud

Subjects
Enterovirus, zoonosis, Central African Republic, vaccine-derived poliovirus, EV-G, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

To characterize enteroviruses (EVs) circulating in farm animals in Central African Republic (CAR), we screened 192 stools of animals under 12 months belonging to family farms located in or near Bangui. To assess whether EV exchanges exist between these animals and humans, we also screened 195 stools of children who lived in contact with farm animals, as well as control stools of 358 children with no contact with farm animals. EVs were typed based on their capsid sequences.In children, all EVs belonged to species A, B and C, with EV-Cs accounting for 60%. Some EV-Cs shared recent common ancestors with lineages of vaccine-derived poliovirus that emerged in the country in 2019–2020. In animals, we identified EV-Gs that belonged to 10 different types, including a previously unknown one that we named EV-G28, while no EV-E or EV-F were observed. The CAR EV-Gs were genetically closely related to specimens sampled in other continents and some of them harboured the torovirus-derived insertion already reported in some EV-Gs. The worldwide circulation of EV-Gs is likely due the massive international trade of live animals. Besides, two human EV-Cs (coxsackievirus A17 and coxsackievirus A24) were detected in pigs, suggesting that these viruses could cross the species barrier. Our work provides original data on the epidemiology and ecology of EVs circulating among herd animals in Africa.

Published
2024
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2. Assessment of HIV viral load monitoring in remote settings in Vietnam - comparing people who inject drugs to the other patients.

Author

Louise H Lefrancois, Binh Thanh Nguyen, Tram Thi Phuong Pham, Nhung Thi Hong Le, Huyen Thi Thanh Dao, Tram Hong Tran, Khanh Phuong Ngo, Ha Thi Tong, Huong Thi Thu Phan, Mohand Ait-Ahmed, Thang Hong Pham, Tuan Anh Nguyen, Fabien Taieb, Yoann Madec, and MOVIDA 2 study group

Subjects
Medicine, Science
Abstract

IntroductionIncreasing access to viral load (VL) monitoring is essential to fight HIV epidemics. In remote settings in Vietnam, using dried blood spot (DBS) sampling for specimen collection could improve the situation. Here, people who inject drugs (PWID) represent many newly antiretroviral therapy (ART)-initiated patients. The goals of this evaluation were to evaluate if access to VL monitoring and the rate of virological failure differed between PWID and non-PWID.MethodsProspective cohort study of patients newly initiated on ART in remote settings in Vietnam. DBS coverage at 6, 12 and 24 months of ART was investigated. Factors associated with DBS coverage were identified through logistic regression, as were factors associated with virological failure (VL ≥1,000 copies/mL) at 6, 12 and 24 months of ART.ResultsOverall 578 patients were enrolled in the cohort, of whom 261 (45%) were PWID. DBS coverage improved from 74.7% to 82.9% between 6 and 24 months of ART (p = 0.001). PWID status was not associated with DBS coverage (p = 0.74), but DBS coverage was lower in patients who were late to clinical visits and in those in WHO stage 4 (p = 0.023 and p = 0.001, respectively). The virological failure rate decreased from 15.8% to 6.6% between 6 and 24 months of ART (pConclusionsDespite training and simple procedures, DBS coverage was not perfect. DBS coverage was not associated with PWID status. Close management is required for effective routine HIV VL monitoring. PWID were more at risk of failure, as were patients who were not fully adherent and patients who were late to clinical visits. Specific interventions targeting these patients are needed to improve their outcomes. Overall, efforts in coordination and communication are essential to improve global HIV care.Trial registrationClinical Trial Number: NCT03249493.

Published
2023
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3. Hospital-based prospective study of pertussis in infants and close contacts in Tehran, Iran

Author

Gaelle Noel, Masoumeh Nakhost Lotfi, Sajedeh Mirshahvalad, Sedaghatpour Mahdi, David Tavel, Seyed M. Zahraei, Roxana Mansour Ghanaie, Tahereh Heidary, Aliahmad Goudarzi, Azardokht Kazemi, Abdollah Karimi, Alireza Nateghian, Mohand Ait-Ahmed, Nicole Guiso, Fereshteh Shahcheraghi, and Fabien Taieb

Subjects
Pertussis, Infant, Whole-cell vaccine, Vaccine compliance, Infection, Diagnosis, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Pertussis remain a global health concern, especially in infants too young to initiate their vaccination. Effective vaccination and high coverage limit the circulation of the pathogen, yet duration of protection is limited and boosters are recommended during a lifetime. In Iran, boosters are given at 18 months and 6 years old using whole pertussis vaccines for which efficacy is not known, and pertussis surveillance is scant with only sporadic biological diagnosis. Burden of pertussis is not well understood and local data are needed. Methods Hospital-based prospective study implementing molecular laboratory testing in infants aged ≤6 months and presenting ≥5 days of cough associated to one pertussis-like symptom in Tehran. Household and non-household contact cases of positive infants were evaluated by comprehensive pertussis diagnosis (molecular testing and serology) regardless of clinical signs. Clinical evaluation and source of infection were described. Results A total of 247 infants and 130 contact cases were enrolled. Pertussis diagnosis result was obtained for 199 infants and 104 contact cases. Infant population was mostly

Published
2021
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4. Circulation of Bordetella pertussis in vaccinated Cambodian children: A transversal serological study

Author

Gaelle Noel, Laurence Borand, Chanthy Leng, Chanthy Keang, Chhunly Botr, Bunnet Dim, Alexandra Kerleguer, Yik S. Peng, Navin Sreng, Vichit Ork, Mohand Ait-Ahmed, Nicole Guiso, and Fabien Taieb

Subjects
Pertussis, Cambodia, Whole-cell vaccine, Sero-prevalence, Timeliness, Infectious and parasitic diseases, RC109-216
Abstract

Background: The Cambodia pertussis immunization schedule includes three doses given at age 6, 10 and 14 weeks using a whole-pertussis vaccine. No booster doses are included. Pertussis biological diagnosis is unavailable in Cambodia and its burden remains unclear. This study aimed to provide accurate data on pertussis serological status of Cambodian children and adolescents, and to evaluate vaccination timeliness. Methods: Fully vaccinated children aged 3–15 years were recruited at the Rabies Prevention Center, Institut Pasteur in Cambodia, Phnom Penh. Capillary blood samples and information on pertussis vaccination history were collected. Anti-pertussis toxin (PT) IgG titers were quantified by ELISA. Results: Compliance with the national immunization schedule was 95.1%. Initiation of vaccination after 8 weeks of age was observed for 29.0% of the children, but was less frequent in the youngest children (13.0%) compared with the oldest ones (46.4%). Rate of children exhibiting anti-PT IgG varied across age groups, and increased from 35.7% to 55.0% in 3–5 and 12–15 years age groups, respectively. Conclusion: Pertussis circulates among vaccinated Cambodian children and adolescents. These data support the need for public health authorities to strengthen pertussis surveillance and use local epidemiological data to make evidence-based decision for the establishment of an optimal vaccination strategy.

Published
2021
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5. Safety and immunogenicity of a measles-vectored SARS-CoV-2 vaccine candidate, V591 / TMV-083, in healthy adults: results of a randomized, placebo-controlled Phase I study

Author

Odile Launay, Cécile Artaud, Marie Lachâtre, Mohand Ait-Ahmed, Jelle Klein, Liem Binh Luong Nguyen, Christine Durier, Bastiaan Jansen, Yvonne Tomberger, Nathalie Jolly, Anna Grossmann, Houda Tabbal, Jérémy Brunet, Marion Gransagne, Zaineb Choucha, Damien Batalie, Ana Delgado, Matthias Müllner, Roland Tschismarov, Pieter-Jan Berghmans, Annette Martin, Katrin Ramsauer, Nicolas Escriou, and Christiane Gerke

Subjects
SARS-CoV-2, COVID-19, vaccine, measles vector, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein. Methods: We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each comprising 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 × 105 median Tissue Culture Infectious Dose [TCID50]), one or two injections of a high dose vaccine (1 × 106 TCID50), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immunogenicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298. Findings: Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment-related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiving the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine. Interpretation: While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development.

Published
2022
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6. Feasibility of dried blood spots for HIV viral load monitoring in decentralized area in North Vietnam in a test-and-treat era, the MOVIDA project.

Author

Tuan Anh Nguyen, Tram Hong Tran, Binh Thanh Nguyen, Tram Thi Phuong Pham, Nhung Thi Hong Le, Dung Viet Ta, Huong Thi Thu Phan, Long Hoang Nguyen, Mohand Ait-Ahmed, Hien Thi Ho, Fabien Taieb, Yoann Madec, and MOVIDA 2 study group

Subjects
Medicine, Science
Abstract

BACKGROUND:Access to HIV viral load is crucial to efficiently monitor patients on antiretroviral treatment (ART) and prevent HIV drug resistance acquisition. However, in some remote settings, access to viral load monitoring is still complex due to logistical and financial constraints. Use of dried blood spots (DBS) for blood collection could overcome these difficulties. This study aims to describe feasibility and operability of DBS use for routine viral load monitoring. METHODS:From June 2017 to April 2018, HIV-infected adults who initiated ART were enrolled in a prospective cohort in 43 clinical sites across 6 provinces in North Vietnam. Following national guidelines, the first viral load monitoring was planned 6 months after ART initiation. DBS were collected at the clinical site and sent by post to a central laboratory in Hanoi for viral load measurement. RESULTS:Of the 578 patients enrolled, 537 were still followed 6 months after ART initiation, of which DBS was collected for 397 (73.9%). The median (inter quartile range) delay between DBS collection at site level and reception at the central laboratory was 8 (6-19) days and for 70.0% viral load was measured ≤30 days after blood collection. The proportion of patients with viral load ≥1000 copies/mL at the 6 month evaluation was 15.9% (n = 59). Of these, a DBS was collected again to confirm virological failure in 15 (24.4%) of which virological failure was confirmed in 11 (73.3%). CONCLUSION:Delay of DBS transfer to the central laboratory was acceptable and most viral loads were measured in ≤30 days, in-line with routine follow-up. However, the level of DBS coverage and the proportion of patients in failure for whom a confirmatory viral load was available were suboptimal, indicating that integration of viral load monitoring in the field requires, among other things, careful training and strong involvement of the local teams. The proportion of patients experiencing virological failure was in line with other reports; interestingly those who reported being non-adherent and those with a low BMI were more at risk of failure.

Published
2020
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8. Dried blood spots perform well to identify patients with active HCV infection in Vietnam

Author

Thai Minh Nguyen, Binh T. Nguyen, Yoann Madec, Fabien Taieb, Trang Thi Thu Nguyen, Tram Thi Phuong Pham, Tuan Anh Nguyen, Hong Thi Bich Mai, Tram Tran, Mohand Ait-Ahmed, Huong Thi Thu Phan, Nhan Thi Do, Hien Ba Pham, National Institute of Hygiene and Epidemiology [Hanoi, Vietnam] (NIHE), Réseau International des Instituts Pasteur (RIIP), Nam Tu Liem District Medical Center [Hanoi], Dong Da General Hospital [Hanoi], Ministry of Health [Hanoi], Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), We would like to thank Abbott Molecular Inc. for providing Abbott RealTime HCV assay reagents, consumables and funding for the study., Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)

Subjects
hepatitis C virus, medicine.medical_specialty, Hepatitis C virus, specificity, Hepacivirus, medicine.disease_cause, Antiviral Agents, Sensitivity and Specificity, Gastroenterology, Specimen Handling, Central laboratory, Limited access, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Need treatment, Humans, Medicine, 030212 general & internal medicine, Dried blood, Hepatology, business.industry, virus diseases, Venous blood, sensitivity, Hepatitis C, digestive system diseases, Confidence interval, viral load, 3. Good health, Infectious Diseases, Vietnam, RNA, Viral, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030211 gastroenterology & hepatology, Dried Blood Spot Testing, business, Viral load
Abstract

International audience; Recently, treatment advances in direct-acting antivirals have radically changed the management of HCV patients. However, in resource-limited countries, identification of patients with active HCV infection is still challenging in remote settings due to the limited access to laboratories able to measure HCV viral load. This study evaluated whether dried blood spots (DBS) transferred to a central laboratory could overcome this challenge. A total of 315 HCV-infected patients, naïve to anti-HCV treatment, provided each three type of samples: plasma, DBS with calibrated quantities of venous blood and DBS with uncalibrated quantities of capillary blood. Qualitative comparison was conducted in terms of detection of HCV viral load on DBS as opposed to plasma to estimate sensitivity and specificity. Quantitative comparisons were conducted by means of correlation estimation. Of the 250 patients with detected plasma HCV viral load, 245 also had detectable DBS HCV viral load (capillary or venous) leading to a sensitivity of 98.0% (95% confidence interval (CI): 95.4%-99.3%); importantly, all measurements with a plasma HCV viral load >118 IU/mL were also detected in DBS. When HCV was not detected in plasma, it was also not detected in DBS resulting in 100% specificity (95% CI: 94.5%-100%). Quantitative HCV viral load results were very similar when utilizing plasma or DBS sample types as illustrated by correlations >0.99. In conclusion, DBS sample types, with either uncalibrated capillary blood or calibrated venous blood, performed well to distinguish patients with active HCV infection, and who therefore need treatment, from other patients.

Published
2020

10. Transversal sero-epidemiological study of Bordetella pertussis in Tehran, Iran

Author

Mohand Ait-Ahmed, Farzad Badmasti, Gaelle Noel, Vajihe S. Nikbin, Fereshteh Shahcheraghi, Yoann Madec, Seyed Mohsen Zahraei, Nicole Guiso, David Tavel, Fabien Taieb, Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris], Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP), Center for Communicable Diseases Control [Iran], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Pôle Intégré de Recherche Clinique (PIRC), The author(s) received no specific funding for this work., Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)

Subjects
0301 basic medicine, Bacterial Diseases, Male, Bordetella pertussis, Bordetella, Whooping Cough, Social Sciences, Iran, Pathology and Laboratory Medicine, Geographical Locations, 0302 clinical medicine, Medical Conditions, Sociology, Seroepidemiologic Studies, Epidemiology, Medicine and Health Sciences, Medicine, Public and Occupational Health, 030212 general & internal medicine, Booster Doses, Child, Pertussis Vaccine, Vaccines, Multidisciplinary, Booster (rocketry), Schools, biology, Age Factors, Vaccination and Immunization, Antibodies, Bacterial, 3. Good health, Bacterial Pathogens, Vaccination, Infectious Diseases, Serology, Medical Microbiology, Child, Preschool, Female, Pathogens, Research Article, medicine.medical_specialty, Asia, Infectious Disease Control, Adolescent, Science, 030106 microbiology, Immunology, Immunization, Secondary, Microbiology, Education, 03 medical and health sciences, Pertussis, Immunity, Environmental health, Humans, Microbial Pathogens, Immunization Schedule, Bacteria, business.industry, Organisms, Biology and Life Sciences, biology.organism_classification, Immunization, Age Groups, Immunoglobulin G, People and Places, Primary immunization, Population Groupings, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Preventive Medicine, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business
Abstract

ObjectivesPertussis remains endemic despite high vaccine coverage in infants and toddlers. Pertussis vaccines confer protection but immunity wanes overtime and boosters are needed in a lifetime. Iran, eligible for the Expanded Program on Immunization that includes the primary immunization, implemented two additional booster doses using a whole-cell vaccine (wPV) at 18 months-old and about 6 years-old. Duration of protection induced by the wPVs currently in use and their impact as pre-school booster are not well documented. This study aimed at assessing vaccination compliance and at estimating the duration of protection conferred by vaccination with wPV in children aged < 15 years in Tehran, Iran.MethodsDetailed information on vaccination history and capillary blood samples were obtained from 1047 children aged 3-15 years who completed the 3 doses-primary pertussis immunization, in Tehran. Anti-pertussis toxin IgG levels were quantified by ELISA.ResultsCompliance was very high with 93.3% of children who received the three primary and 1st booster doses in a timely manner. Timeliness of the 2nd booster was lower (63.3%). Rate of seropositive samples continuously and significantly increased from 1-2 to 5-6 years after 1st booster attaining 30.4% of children exhibiting serological sign of recent contact with B. pertussis. Second booster dating back 1 or 2 years was associated with high antibody titers, which significantly decreased within 3 years from injection. Among children who received 2nd booster injection more than 2 years before serum analysis, seroprevalence of pertussis infection was 8.4% and seropositivity rate was higher from the 10 years-old group.ConclusionSeropositivity in children aged 6-7 years with no 2nd booster supports the need for a vaccination at that age. Adolescent booster may also be considered.

Published
2020

11. Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort)

Author

Yannick Bacq, Victor de Ledinghen, Gérard Thiéfin, Claire Wartelle, Marc Bourlière, Sylvie Chevret, Lawrence Serfaty, Christophe Pilette, Jean-Pierre Zarski, S. Allam, Denis Ouzan, Dominique Guyader, Yves Benhamou, Jean-Didier Grangé, Cendrine Chaffaut, Jean-Marie Péron, Dominique Larrey, Ariane Mallat, Dominique Roulot, Fabien Zoulim, Dominique Capron, Odile Goria, Catherine Buffet, Vincent Di Martino, Jean-Pierre Bronowicki, Armand Abergel, Christine Silvain, Sophie Hillaire, Mohand Ait Ahmed, Pierre Nahon, Stanislas Pol, Christos Christidis, Valérie Bourcier, Jean-Claude Trinchet, Thong Dao, Jean-Frédéric Blanc, Laurent Alric, Albert Tran, Paul Calès, Philippe Mathurin, Patrick Marcellin, Service d'Hépato-gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Cellules souches normales et cancéreuses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut Arnaud Tzanck, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Département digestif, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), CHU Rouen, Normandie Université (NU), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Huriez-Université de Lille, Inserm, UMR-1053, Université de Bordeaux, Bordeaux, F-33076, France, Centre hospitalier universitaire de Bordeaux, Department of Hepatology, Hôpital Saint-André, Bordeaux, F-33076, France, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d'hépatologie [Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hopital d'Aix en Provence, Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Attention, Orientation et Chronobiologie (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Le Mans (CH Le Mans), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hépatogastroentérologie, CHU Amiens-Picardie, Institut Mutualiste de Montsouris (IMM), Hôpital Foch [Suresnes], Hôpital JeanMinjoz, Service d'hépato-gastroentérologie, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et épidemiologie clinique, Agence Nationale de Recherches sur le Sida et les Hepatites Virales, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA)-CHU Grenoble, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, CHU Nice, Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques ( HIFIH ), Université d'Angers ( UA ), Hepato-gastro-enterology, Toulouse University hospital, Pharmacochimie et Pharmacologie Pour le Développement ( PHARMA-DEV ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique ( CNRS ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Centre Hospitalier Universitaire Estaing, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Service de gastro-entérologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service d'Hépato-Gastro-Enterologie et Nutrition [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Mobilités : Attention, Orientation et Chronobiologie ( COMETE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Assistance publique - Hôpitaux de Paris (AP-HP), Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Jean Verdier [AP-HP], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'hépatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépatologie et de Gastroentérologie [Lyon], Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Saint-André, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Institut mutualiste Monsouris (IMM), CHU Saint-Eloi-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Service d'Hépato-gastro-entérologie [CHU Saint-Antoine]

Subjects
Liver Cirrhosis, Male, Cirrhosis, [SDV]Life Sciences [q-bio], Hepatocellular / physiopathology, Liver Neoplasms / mortality, medicine.disease_cause, Gastroenterology, Cohort Studies, Liver disease, Cause of Death, Liver Cirrhosis / complications, Longitudinal Studies, Prospective Studies, Prospective cohort study, Liver Failure / mortality, Hepatocellular / virology, Liver Neoplasms, Hepatitis C / complications, Middle Aged, Hepatitis B, Hepatitis C, 3. Good health, Hepatocellular carcinoma, Disease Progression, Female, France, Liver cancer, Hepatitis C / pathology, Hepatitis B / pathology, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Liver Neoplasms / pathology, Milan criteria, Risk Assessment, Liver Cirrhosis / virology, Predictive Value of Tests, Internal medicine, Liver Failure / pathology, medicine, Humans, Decompensation, Hepatitis B / complications, Proportional Hazards Models, Hepatitis B virus, Liver Failure / virology, Analysis of Variance, Hepatology, [ SDV ] Life Sciences [q-bio], business.industry, Carcinoma, medicine.disease, Survival Analysis, digestive system diseases, Liver Neoplasms / virology, Liver Cirrhosis / mortality, Multivariate Analysis, Hepatocellular / mortality, business, Liver Failure
Abstract

International audience; Various critical events, liver related or not, occur in patients with compensated cirrhosis, but their respective burden remains to be prospectively assessed. The aim of this prospective cohort study involving 35 French centers was to capture the whole spectrum of complications occurring in compensated viral cirrhosis (VC) using competing risks analyses. Inclusion criteria were: histologically proven cirrhosis resulting from hepatitis C virus (HCV) or hepatitis B virus (HBV); Child-Pugh A; and no previous hepatic complications. The cohort was considered as a multistate disease model, cumulative incidences (CumIs) of events were estimated in a competing risks framework. A total of 1,654 patients were enrolled from 2006 to 2012 (HCV, 1,308; HBV, 315; HCV-HBV, 31). During a median follow-up of 34 months, at least one liver nodule was detected in 271 patients, confirmed as hepatocellular carcinoma (HCC) in 128 (4-year cumI: 10.5%) and cholangiocarcinoma in 3. HCC incidence was higher in HCV (4-year cumI: 11.4% vs. 7.4%; P = 0.05). HCC fulfilled Milan criteria in 79.3%, leading to curative treatment in 70.4%. Liver decompensation occurred more frequently in HCV patients (4-year cumI: 10.8% vs. 3.6%; P = 0.0004). Virological eradication/control was achieved in 34.1% of HCV and 88.6% of HBV patients and was associated with a marked decrease in HCC, decompensation, and bacterial infection incidences. Survival was shorter in HCV patients (4-year cumI: 91.6% vs. 97.2%; P = 0.0002). Death (n = 102; missing data: 6) was attributed to liver disease in 48 (47%; liver cancer: n = 18; miscellaneous, n = 30) and extrahepatic causes in 48 (47%; bacterial infection: n = 13; extrahepatic cancers: n = 10; cardiovascular events: n = 5; miscellaneous, n = 20). CONCLUSION: After 3 years of follow-up, extrahepatic events still explained half of deaths in patients with compensated VC. A strong decrease in complications was linked to virological eradication/control. (Hepatology 2015;62:737-750)

Published
2015

12. Transversal sero-epidemiological study of Bordetella pertussis in Tehran, Iran.

Author

Gaelle Noel, Farzad Badmasti, Vajihe S Nikbin, Seyed M Zahraei, Yoann Madec, David Tavel, Mohand Aït-Ahmed, Nicole Guiso, Fereshteh Shahcheraghi, and Fabien Taieb

Subjects
Medicine, Science
Abstract

ObjectivesPertussis remains endemic despite high vaccine coverage in infants and toddlers. Pertussis vaccines confer protection but immunity wanes overtime and boosters are needed in a lifetime. Iran, eligible for the Expanded Program on Immunization that includes the primary immunization, implemented two additional booster doses using a whole-cell vaccine (wPV) at 18 months-old and about 6 years-old. Duration of protection induced by the wPVs currently in use and their impact as pre-school booster are not well documented. This study aimed at assessing vaccination compliance and at estimating the duration of protection conferred by vaccination with wPV in children aged < 15 years in Tehran, Iran.MethodsDetailed information on vaccination history and capillary blood samples were obtained from 1047 children aged 3-15 years who completed the 3 doses-primary pertussis immunization, in Tehran. Anti-pertussis toxin IgG levels were quantified by ELISA.ResultsCompliance was very high with 93.3% of children who received the three primary and 1st booster doses in a timely manner. Timeliness of the 2nd booster was lower (63.3%). Rate of seropositive samples continuously and significantly increased from 1-2 to 5-6 years after 1st booster attaining 30.4% of children exhibiting serological sign of recent contact with B. pertussis. Second booster dating back 1 or 2 years was associated with high antibody titers, which significantly decreased within 3 years from injection. Among children who received 2nd booster injection more than 2 years before serum analysis, seroprevalence of pertussis infection was 8.4% and seropositivity rate was higher from the 10 years-old group.ConclusionSeropositivity in children aged 6-7 years with no 2nd booster supports the need for a vaccination at that age. Adolescent booster may also be considered.

Published
2020
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13. Safety and immunogenicity of a synthetic carbohydrate conjugate vaccine against Shigella flexneri 2a in healthy adult volunteers: a phase 1, dose-escalating, single-blind, randomised, placebo-controlled study

Author

Philippe J. Sansonetti, Armelle Phalipon, Jacob Atsmon, Anya Bialik, Alexandra Dorman, Shiri Meron-Sudai, Cecile Artaud, Carla W G Hoitink, Shai Ashkenazi, Valeria Asato, Arava Reizis, Marie-Lise Gougeon, Laurence A. Mulard, Ortal Ariel-Cohen, Dani Cohen, Sophy Goren, Janny Westdijk, Tel Aviv University (TAU), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Translational Vaccinology (INTRAVACC), Ariel University, Pathogénie microbienne moléculaire, Chimie des Biomolécules - Chemistry of Biomolecules, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and This Article is dedicated to the late John B Robbins and to Rachel Schneerson formerly at the National Institute of Child Health and Human Development, National Institutes of Health, for their groundbreaking achievements and inspiring visionary leadership in the field of shigella glycoconjugate vaccine development. We thank the members of the Centre de Recherche Translationnelle—Coordination Clinique, Institut Pasteur: Mohand Ait Ahmed for his help in site trial implementation, Nathalie Jolly for helpful discussions about trial conduct, and Hélène Lafolly for her help at the early stages of the clinical project. We acknowledge Odile Launay (CIC Cochin Pasteur), Beatrice De Vos (Consultant), and Eli Somekh (Wolfson Medical Center) for agreeing to be members of the independent data monitoring committee.

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Population, Dose-Response Relationship, Immunologic, Placebo-controlled study, Aluminum Hydroxide, Placebo, Injections, Intramuscular, Shigella flexneri, Young Adult, 03 medical and health sciences, Immunogenicity, Vaccine, 0302 clinical medicine, Adjuvants, Immunologic, Shigella Vaccines, Conjugate vaccine, Internal medicine, Humans, Medicine, media_common.cataloged_instance, Single-Blind Method, 030212 general & internal medicine, European union, education, Adverse effect, Dysentery, Bacillary, media_common, Vaccines, Synthetic, education.field_of_study, Vaccines, Conjugate, business.industry, Immunogenicity, O Antigens, Middle Aged, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Antibodies, Bacterial, Healthy Volunteers, 030104 developmental biology, Infectious Diseases, Tolerability, Female, business
Abstract

Shigella remains in the top four pathogens responsible for moderate to severe diarrhoea in children below 5 years of age. The shigella O-specific polysaccharide (O-SP) is a promising vaccine target. We developed a conjugate vaccine prototype incorporating a unique well defined synthetic oligosaccharide hapten, chemically designed for optimal antigenic, conformational, structural, and functional mimicry of the O-SP from Shigella flexneri 2a (SF2a). We aimed to assess the safety, tolerability, and immunogenicity of this original synthetic oligosaccharide-based vaccine candidate, SF2a-TT15, conceived to drive the antibody response towards the key protective determinants of the native lipopolysaccharide antigen, in a first-in-human phase 1 study.We did a first-in-human, dose-escalating, single-blind, observer-masked, randomised, placebo-controlled study at the Clinical Research Center of Tel Aviv Sourasky Medical Center (Israel). Participants were healthy adults aged 18-45 years with low titres of serum SF2a-specific IgG antibodies. 64 eligible participants were assigned to one of two cohorts. 32 participants in each of the two cohorts were randomly assigned via computer-generated algorithm in a stepwise manner to receive the 2 μg (cohort 1) and 10 μg oligosaccharide dose (cohort 2) of the SF2a-TT15 vaccine candidate non-adjuvanted or adjuvanted with aluminium hydroxide (alum) or matching placebos. The vaccine was administered as three single intramuscular injections into the arm, 28 days apart. The primary outcome was the incidence and severity of adverse events, which were assessed in the intention-to-treat safety population analysis including all participants who were randomly assigned and received at least one vaccine or placebo injection. The immunogenicity endpoints were secondary outcomes and were analysed in all participants who were randomly assigned, received all of the assigned injections before the time of the immunogenicity assessment, and provided blood samples for immunological follow-up (per-protocol immunogenicity analysis). The study is registered with ClinicalStudies.gov, NCT02797236 and is completed.Of 203 volunteers initially screened, 64 participants were enrolled between Sept 20, 2016, and Sept 26, 2017. In each of the two cohorts, 12 participants received the adjuvanted vaccine, 12 received the non-adjuvanted vaccine and eight received the matching placebo (four each). The SF2a-TT15 glycoconjugate was well tolerated at both doses. No serious or severe adverse events occurred. Overall, seven (88%) of eight to 12 (100%) of 12 in each group of volunteers had one adverse event or more after receiving the study agents with the majority of adverse events, 300 (98%) of 307, considered mild in intensity. Of the seven adverse events defined as moderate in severity, one (nausea) was suspected to be related to the vaccine candidate. At all post-immunisation days and for both oligosaccharide doses, whether adjuvanted or not, SF2a-TT15 induced significantly higher serum IgG anti-SF2a lipopolysaccharide geometric mean titres (GMTs) as compared with baseline or with the corresponding GMTs in placebo recipients (p0·01). After one injection, the non-adjuvanted 10 μg oligosaccharide dose induced a 27-times increase in IgG GMT (5080 vs 189) and the non-adjuvanted 2 μg oligosaccharide dose induced a five-times increase (1411 vs 283), compared with baseline. Alum enhanced the specific IgG response at 2 μg oligosaccharide dose after the third injection (GMTs 3200 vs 1176, p=0.045).SF2a-TT15 was safe and well tolerated and induced high titres of anti-SF2a LPS IgG antibodies. These results support further evaluation of this original synthetic oligosaccharide-protein conjugate vaccine candidate for safety, immunogenicity, and protective efficacy in target populations.The European Union Seventh Framework Programme.

Published
2021

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