November 27-28 2024
Lyon, France
November 27-28 2024
Lyon, France
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Laure Delhon
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Roche Pharma Research and Early Development, Cardiovascular, Metabolism, Immunology, Infectious Diseases and Ophthalmology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. – Basel (Switzerland)
Zosurabalpin (RG6006) is the first representative of a novel class of tethered macrocyclic peptide (MCP) antibiotics. It possesses a differentiated mode of action and is active exclusively against Acinetobacter spp., including carbapenem-resistant Acinetobacter baumannii calcoaceticus complex (ABC) organisms.
In the talk, we will present the discovery and optimization of this compound class culminating in the selection of the clinical candidate zosurabalpin.
Zosurabalpin has a potent in vitro activity against all clinical ABC isolates tested to date. In vivo efficacy has been confirmed in multiple models of infections induced by A. baumannii, including neutropenic murine thigh and lung infection models and immunocompetent murine model of sepsis.
We will also describe how we arrived at the hypothesis and validation of the zosurabalpin molecular target that is responsible for the trafficking of bacterial lipopolysaccharide (LPS) from its synthesis origin in the cytoplasm to the bacterial outer membrane. Data on the resistance profiling of zosurabalpin will also be discussed.
Zosurabalpin is currently in phase 1 clinical trials, and has the potential to become the first antibiotic of a new class in more than 50 years to be used against infections caused by gram-negative bacteria. This project has been funded in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under OT number: HHS0100201600038C.
Claudia has been in the field of Antibiotics R&D since 2005. She is a Molecular Biologist by training with a PhD in BioPharmaceutical Microbiology obtained in 2002 from University of Catania (IT) followed by research stays at the University of Camerino (IT) and Technical University of Denmark. She started her industrial career in Basel, CH, in 2005 working initially in Biotech (Arpida, Polyphor) and afterwards in Pharma, joining Roche antibiotics R&D in 2013. During these years in industry, Claudia served as discovery project leader & non-clinical pharmacology cross-functional expert in advanced programs, including iclaprim, murepavadin and nacubactam. While being in Roche she led the zosurabalpin project from discovery to the stage of entry into clinic. In parallel she is currently leading the translational microbiology team and co-leads the Roche antibiotics discovery team.
The Brodin lab develops and applies system immunology approaches to study human immune system variation in health and disease and human immune system development early in life. This involves measurements of all white blood cells at once in miniaturized blood samples and estimating the cell-cell interactions giving rise to any immune response in humans. The work of the group involves the elucidation of heritable and non-heritable factors that shape human immunity, immune system development and adaptation to microbial factors early in life as well as a research program in clinical application of systems immunology in children to diagnose and describe immune system dysregulation and enable precision medicine. Here professor Brodin will describe recent results involving sex differences in human immune systems as well as early life exposures shaping immunity in humans
Petter Brodin is Garfield Weston Chair and Professor of pediatric immunology at Imperial College London and professor of Pediatric immunology at Karolinska Institutet in Stockholm, Sweden. The Brodin lab (https://brodinlab.com/) develops and applies novel experimental and computational methods to describe human immune systems with a particular interest in the immune systems of children, its development early in life, and its regulation in health and disease.
The rise of antibiotic-resistant infections demands innovative approaches beyond traditional antibiotics. Bacteriophages, or phages, have emerged as a promising alternative, uniquely capable of targeting harmful bacteria without affecting beneficial microbes. Their rapid bacterial lysis makes phages ideal for both personalized and broad-spectrum therapies in combating multidrug-resistant infections. However, challenges such as biological variability, limited host range, and clinical scalability remain to be overcome.
Fagoterapia Lab, Italy’s first startup dedicated to bacteriophage research, addresses these challenges by combining a comprehensive phage biobank with advanced AI algorithms to design personalized treatments. This approach allows for the prediction of effective phage combinations, establishing personalized phage therapy as a viable clinical option. This presentation will explore the scientific and clinical potential of phage therapy, underscoring its role as a leading strategy in the fight against antimicrobial resistance.
Giuseppe Maccari is Chief of IT at Fagoterapia Lab (Pisa, Italy) and senior bioinformatician and coordinator of the data science unit at Toscana Life Sciences Foundation (Siena, Italy). He earned his degree in Molecular Biological Sciences from the University of Pisa and completed a Ph.D. in Experimental Medicine and Oncology at the University of Insubria in 2011. Previously, he was a postdoctoral researcher at the Italian Institute of Technology, developing statistical models for cell-penetrating peptides and antimicrobial peptides in cellular transport systems. He has also collaborated with the European Bioinformatics Institute (EBI) to enhance the global database for studying the histocompatibility complex. His expertise includes data analysis, molecular dynamics, and machine learning applied to protein-protein interactions.
The antibiotics market urgently requires transformative innovation to combat resistance development and ensure future-proof solutions. Traditional small molecules and derivatives, while helpful, are not sustainable long-term due to rapid resistance development. Instead, disruptively new solutions are needed.
Obulytix addresses these needs with next-generation phage-derived lysins, precision antibiotics evolved by bacteriophages to degrade peptidoglycan and lyse bacterial cells. Phage lysins show low resistance development probability, no cross-resistance with known mechanisms, species-level tunable specificity, and rapid bactericidal effects against persisters and biofilms. Their hallmark feature is the customization potential, allowing for tailored solutions against any pathogen through recombinant shuffling of lysin building blocks.
Obulytix has automated this tailoring process with a hit-to-lead development platform. The platform’s three cornerstones are the VersaTile technology for creating millions of variants, an advanced automated screening platform, and dedicated AI tools for intelligent analysis. Obulytix is developing next-generation lysins active against Gram-negative bacteria with suitable PK/PD properties for IV use, a combination absent in earlier generations of phage-derived lysins.
Yves Briers is CSO of Obulytix and an Associate Professor at the department of Biotechnology of Ghent University (Belgium). He has pioneered phage lysin research for 20 years, performing both fundamental and applied research to develop phage lysin-based antibiotics. In July 2023 he founded with three co-founders Obulytix, spinning out core technology for hit-to-lead development of phage lysins. Obulytix aims to revolutionize the fight against antimicrobial resistance with this proprietary development platform. Yves Briers also co-founded the Belgian Society for Viruses of Microbiology in 2022, which he currently chairs.
Pandemics present significant challenges to global health security. International trade and travel can drive the rapid spread of diseases. To address these threats, countries must adopt comprehensive strategies for public health preparedness. Fabentech plays a critical role in this effort by providing medical countermeasures to bolster global health resilience against these emerging risks.
Fabentech has an established track record in creating countermeasures for pathogens such as H5N1 avian influenza, Ebola, and Crimean-Congo hemorrhagic fever (CCHF). Currently, the company is advancing the development of a treatment for Nipah virus, a zoonotic disease characterized by an exceptionally high mortality rate.
Fabentech’s solutions rely on highly purified polyclonal antibodies fragments which offer broad protection against multiple viral variants, making them a robust solution against rapidly mutating pathogens. Our recent results show that FabenCOV, a medical countermeasure developed to combat COVID-19 in patients at risk of developing severe disease remains effective at cross-neutralizing the recent JN-1 variant even after four years of viral evolution contrary to mAbs which totally lost their efficacy in the course of the pandemy.
Looking to the future, Fabentech is developing new broad-spectrum antibodies using an innovative mosaic antigen. This novel method will produce mutivalent polyclonal antibodies capable of recognizing both current and future zoonotic sarbecoviruses, which pose a pandemic threat. As part of the e-FabRIC European collaborative project, Fabentech aims to advance these antibodies as a critical tool in the fight against emerging viral threats.
This forward-thinking strategy positions Fabentech at the forefront of pandemic preparedness, with the potential to deliver future pan-viral countermeasures essential for global health security.
This research was made possible through funding from the 2030 Emerging Infectious Diseases program, BPI France, and the Horizon Europe initiative.
Caroline Ballet is scientific project leader at Fabentech in the department of emerging infectious disease preparedness. Since she received her PhD in immunology in 2008 at the University of Nantes, she spent 15 years coordinating projects in the field of transplantation, oncology and infectious disease in biotechnology companies and served as project leader in several national and international consortia. She is the scientific coordinator of the HORIZON EUROPE funded e-FabRIC consortium lead by Fabentech.
Administration of monoclonal antibodies (mAbs) has emerged as a pivotal strategy for the treatment and prevention of infectious diseases. Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope protein (Env) can prevent infection in animal models and are used for passive immunization in clinical trials. Moreover, bNAbs have been demonstrated to effectively suppress viremia and delay viral rebound after interruption of antiretroviral therapy (ART) in HIV-1-infected individuals. Finally, they have become a critical component for experimental approaches to achieve HIV-1 functional cure. While recent results strengthen the high potential of bNAbs, pre-existing or de novo HIV-1 resistance can cause treatment failure. Therefore, defined strategies are needed to provide clinically effective antibody-mediated treatment approaches for people living with HIV-1.
Florian Klein is director of the Institute of Virology and full professor at the University of Cologne, Germany. His research focuses on the development of human B lymphocytes and antibodies, with a particular interest in the humoral immune response to viral pathogens, such as HIV-1, SARS-CoV-2, Ebola- and Cytomegaloviruses. Together with his team, he employs advanced single cell technologies and investigates in detail antibody-virus interactions. In addition, his team focuses on the development of monoclonal antibodies to prevent and treat viral infections. To this end, his team conducts early-phase clinical trials to translate basic laboratory findings into clinical applications.
Associations between the human microbiome and immune-mediated diseases are increasingly made, however, potential treatment options targeting the microbiota are still not translated to patients with immune-mediated diseases.
Our laboratory has made progress towards host-microbiota mechanisms that may aid in developing future therapeutic avenues. We previously demonstrated that the gut pathobiont E. gallinarum translocates to lymph nodes, liver, and spleen causing lupus like disease in mice. Importantly, this bacterium is detectable in human liver of lupus patients but does not cause typical signs of infection. In autoimmune prone hosts it rather breaches immunologic tolerance to self.
Vaccination against pathobionts is an attractive option, which we have shown can prevent systemic autoimmunity in mice. Intramuscular vaccine against E. gallinarum suppresses translocation, leading to reduced autoimmune pathology, representing a new paradigm for vaccine-based approaches in autoimmunity.
Furthermore, dietary approaches can modulate the gut microbiota and can improve rheumatoid arthritis.
Lastly, other groups have shown that bacteriophage therapy targeting specific pathogens showed promise in treating inflammatory bowel disease in mice and was tolerated in first-in-human studies with phages against Klebsiella pneumonia.
Altogether, these microbiota targeting therapies are breaking new ground in the treatment of autoimmunity and may synergize with therapies targeting the immune system.
Carina Brune is a PhD student in Prof. Martin Kriegel’s Group at the Department of Translational Rheumatology and Immunology at the University of Münster, Germany. The lab’s research focusses on the interplay between the translocating microbiota and autoimmune disorders. For her PhD project about host-microbiota interactions in autoimmunity, she was awarded a scholarship by the German Academic Scholarship Foundation.
Ms. Brune earned her Pharmacy degree from the University of Münster in 2023. Due to her academic achievements, her studies were also supported by a scholarship from the German Academic Scholarship Foundation. To further explore her research interests in the microbiome field, Brune undertook research internships at both the Thaiss Lab and Helfrich Lab located at the University of Pennsylvania, USA, and Goethe University Frankfurt, Germany, in 2021 and 2022, respectively.
Reduced vaccine effectiveness is associated with an incorrect balance between pro-inflammatory and anti-inflammatory cytokines, such as IL-10. Inflammation is regulated at the level of transcription, ultimately controlled by the epigenetic state of chromatin. Long non-coding RNAs (lncRNAs) regulate chromatin state and represent a novel druggable class of molecules to achieve durable epigenetic silencing of target genes. Trained immunity (TI) is a process that results in the long-term epigenetic reprogramming of innate immune cells that improves protection against infections and enhances BCG vaccine responses. Several TI-related cytokines, including IL-1β, TNF, and IL-6, are regulated by a family of lncRNAs called Immune Priming LncRNAs (IPLs). Recent research identified the lncRNA AMANZI, which negatively regulates IL-1β by modulating chromatin loops and coordinates anti-inflammatory responses via IL-37, revealing a biphasic circuit controlling inflammation. Lemba has identified and characterized IPLs, including AMANZI, regulating pro- and anti-inflammatory factors critical to TI and vaccinology. Utilizing our proprietary platform, MOSAIC, we identified antisense oligonucleotides (ASOs) that target lncRNAs such as AMANZI to enhance IL-1B production and reduce IL-37, shifting the cytokine balance to correlate positively with BCG vaccine-mediated protection. The lncRNA-based epigenetic modulation represents a powerful method for fine-tuning cytokine levels to maximize vaccine efficacy.
Stephanie is the Chief Scientific Officer of Lemba Therapeutics. She has over 15 years of experience in lncRNA biology and has made key discoveries on the role of nuclear architecture, lncRNAs and epigenetic regulation in trained immunity and inflammation. Lemba has built the MOSAIC platform to translate lncRNA biology into therapeutics. MOSAIC incorporates functional genomics, AI proprietary target discovery and high throughput phenotypic screening to identify antisense oligonucleotides (ASOs) capable of functionally modulating lncRNAs. MOSAIC has been used to identify lncRNAs targets and develop ASO lead candidates for a range of indications including osteoarthritis, drug-resistant solid tumors and to act as epigenetic modulators of vaccine responses.
Analyzing kinetic rates is crucial for optimizing the effectiveness and safety of immunotherapeutic agents like antibodies. The targets of therapeutic antibodies are often transmembrane proteins, and their native environment influences binding kinetics. This study explores the predictive nature of kinetic rates in understanding the in vivo mode of action of antibodies.
First, we examined the binary and ternary binding modes of the bispecific antibody emicizumab. Utilizing a specialized Y-shaped DNA nanostructure to immobilize both antigens on a biosensor surface, we mimicked the cell surface conditions as the antigens were presented with optimal accessibility and defined stoichiometry. Two-color fluorescence detection allowed us to discern affinity and avidity-binding modes, providing insights into emicizumab’s in vivo mode of action.
In the second case study, single-cell Interaction Cytometry (scIC) was employed to measure antibody binding kinetics directly on cells. Cell immobilization on the sensor surface was achieved using flow-permeable polymer cages, enabling observation of binding interactions within the cellular membrane’s native environment. Applying scIC, we investigated the real-time binding kinetics of anti-HER2 antibodies with their targets directly on breast cancer cells and identified differences in binding kinetics on cells with high or low target receptor expression.
Anahi studied Nanosciences and Nanotechnology at KU Leuven, Belgium and at University Grenoble Alpes, France. In her master thesis she studied electrochemical biosensors, before working as a research scientist at the Institute of Photonic Sciences in Barcelona, Spain, where she acquired experience in optical biosensors. Currently, she is developing innovative assays for the investigation of DNA/RNA-binding proteins and nucleic acid-modifying enzymes.
The abstract for this presentation is currently unavailable.
The abstract for this presentation is currently unavailable.
Background: Respiratory infections, both acute and chronic, represent the third cause of morbidity and mortality worldwide. Among the pathogens responsible for those infections, multi-drug resistant Pseudomonas aeruginosa has raised major concern, due to its capacity to cause a wide-array of infections in individuals with compromised immune defenses and to withstand standard-of-care therapeutic treatments. Since their development, antibody-based approaches have proven to be efficient in the treatment of diverse infections. We propose here a novel antibody-based approach harnessing the complement, the primary defense mechanism in anti-infective immunity, as we investigate its immune system-activating properties.
Project description: We developed tetrameric proteins to activate the complement system in a target-dependent way. A moiety targeting the pathogen is complexed to an effector function through the oligomerization domain of the C4 binding protein. Complement-activating Multimeric immunotherapeutic compleXes, or CoMiX, target the Psl-exopolysaccharide of the bacterium and activate either the classical (dimeric Fc-region, CoMiX-Fc) or the alternative (Factor H-related protein 1 competing with the complement inhibitor Factor H (CoMiX-FHR1) complement pathway. In vitro, and in presence of human serum, CoMiX induced C3b and C5b9 deposition on the bacterium, leading to either its direct killing or its early opsonisation and subsequent phagocytosis by macrophages. In addition, CoMiX protected human epithelial cells against P. aeruginosa-induced cytotoxicity. Importantly, CoMiX administered intranasally to acutely infected mice, significantly decreased bacterial burden through the higher induction of local complement pathways and reduced lung inflammation, including innate immune cells and pro-inflammatory mediators, leading to the survival of 90-100% of the mice, in comparison to control animals (0-30% survival).
Innovative strength and applications: The innovative feature of our antibody-based molecules lies in their capacity to stimulate the complement directly at the surface of the pathogen/the site of infection, preserving the protective commensal bacteria. The innate immune response is rapid, and crucial for anti-bacterial host defense, allowing the killing of bacteria before the set-up of resistance strategy by the pathogen. The noteworthy advantages of our technology are: (1) its production in mammalian cells allowing the use of post-translational modifications, (2) its versatility to modify the targeting system or the effector functions, (3) a conceivable bi-targeted approach that could be used against co-infections, and (4) the possibility to generate tetrameric-drug conjugates by adding a drug in between the targeting and effectors moieties. Beside our proof-of-concept on P. aeruginosa infection model, we already successfully developed CoMiX targeting a binding domain of Neisseria gonorrhoeae, a bacteria quite sensitive to the complement system, or against Aspergillus fumigatus, a deadly airways fungus.
Conclusion: Our versatile technology opens novel perspectives for the design of targeted anti-infective molecules to treat both acute and chronic infections by harnessing the complement system. Subsequent research and clinical development are now essential to comprehensively assess their potential benefits in patients.
Dr. Aubin Pitiot conducts translational studies by focusing his research on the response of the host immune system against infectious diseases, as well as the development of new therapeutics to prevent and/or treat them. He obtained a PhD in Health Sciences and Immunology, investigating the modulation of the immune system by therapeutic antibodies (University of Tours) and is actually undergoing a post-doctorate on the development of antibody-based proteins harnessing innate immunity (Luxembourg Institute of Health).
Background: The COVID-19 pandemic has demonstrated the urgent need to develop versatile vaccination platforms that could be quickly implemented for infectious diseases and to respond promptly to future pandemic outbreaks. It is of utmost importance to provide a vaccine in a time- critical manner for such diseases, as the frequency of such epidemics and pandemics as we see them today, will be heavily increasing due to rise in global travel, global warming, increase in population density, penetration into previously uninhabited areas and animal trade. Nucleic acid vaccines, such as those based on mRNA are endowed of these features.
Offer/project description: To address the urgent need to find solutions to the SARS-CoV-2 Pandemic, Takis has developed COVID-eVax, a vaccine approach based on genetic engineering and DNA electroporation as part of the X-eVax platform, previously developed. The project started in 2020 and consisted of the molecular design of the vaccine, the development of the reagents and tests necessary to test its effectiveness and the experiments in animal models. Subsequently, GMP-grade material (Good Manufacturing Practices) was produced, all regulatory studies were conducted (toxicology, biodistribution, immune response) and finally a phase 1 study in humans, which ended in December 2021, achieving all the objectives set and providing the basis for evaluations in other applications. DNA vaccines advantages are: (1) simple and quick production of DNA encoding the antigens by PCR or synthetic methods (potential game-changers for new variants especially vaccine resistant strains), (2) easy large-scale production, (3) safety compared to inactivated virus vaccines, and (4) higher thermostability (minimal cold-chain requirements), which is an issue with some vaccines. The DNA-based platforms offer great flexibility in manipulating the encoded vaccine antigen and have a great potential for accelerated development. Recently, the first DNA vaccine against SARS-CoV-2 (ZyCov-D) has been registered in India for human use; moreover, DNA vaccines have been extensively tested in multiple clinical trials in the oncology field and are commonly used in veterinary medicine.
Innovative strength & Applications: DNA-based vaccines (as opposed to mRNA-based vaccines) are stable, do not require cold-chain supply, and can easily be produced in large amounts in bacteria. All these advantages make this platform technology an attractive tool, as it overcomes several shortcomings of alternative approaches (e.g., complex production processes, stability issues, purchase price). Besides the classical plasmid form of DNA, we have also developed a linear form of DNA, encoding only for the antigen of interest. This novel form of nucleic-acid vaccine has already proven to be efficacious in preventing SARS-CoV-2 infection in feline and ferret animal model.
Conclusion: Takis has developed an innovative BSL3 biomodule to perform customized in vitro and in vivo research activities with high-risk pathogens. This new structure will offer the opportunity to develop and test genetic vaccines against BSL-3 pathogens in order to answer promptly to future pandemics.
I am a PhD scientist specialized in translational research in immunology, pathology, virology and oncology field. Currently I have the role of Principal investigator at Takis Biotech and I am responsible for the management of preclinical and clinical research projects, aiming to develop candidate immunotherapies for human and veterinary applications. My background is mainly in the immunology field and I have strong experience in academic, clinical and industrial environment.
Background: BK polyomavirus (BKPyV) is a ubiquitous virus with a prevalence of around 90% in the adult population worldwide. After infection, the virus diffuses hematogenously and subsequently persists in the renal epithelium. Several subtypes of BKPyV exist with varying prevalence in different world regions. Although generally silent in immunocompetent individuals, BKPyV can be pathogenic in a context of immunosuppression. In kidney transplant patients, BKPyV replication can lead to nephropathy and a return to dialysis, whereas in marrow transplant patients, BKPyV is one of the viruses responsible for haemorrhagic cystitis. As BKPyV replication is induced by excessive immunosuppression, and given that no effective antiviral treatment exists, BK virus-induced nephritis can only be preemptively avoided by reducing the immunosuppressant treatment. In the first-year post-kidney transplantation, screening for BK polyomavirus (BKPyV) is frequently recommended but there is no point-of-care assay on the market to detect this viral replication. Currently, BKPyV can only be screened using nucleic acid quantification tests and no antigen detection tests being available. Moreover, PCR results are frequently observed in the urine of transplanted patients for variable periods without significantly affecting their renal function. These overdiagnosis lead to therapeutic intervention, by reducing immunosuppression, but entailing the concomitant risk of graft rejection. In the context of bone marrow transplantation, the challenge is slightly different and the clinician needs to rapidly identify the virus causing haemorrhagic cystitis.
Offer/project description: In this context, SPyDiag has developed for the first time a lateral flow immunoassay (LFIA) and both an enzyme-linked immunosorbent assay (ELISA) based on patented antibodies directed against the major structural antigen (VP-1) of the different BKPyV genotypes (US2022396612 (A1) – new antibody targeting the VP-1 protein). This viral antigen detection truly indicates the replication of BKPyV. We studied the applicability and relevance of these assays as a new diagnostic method to detect and quantify specifically BKPyV replication in kidney and bone marrow transplantation.
Innovative strength and application : Initially, the VP1 antigen was detectable in cell culture samples, BKPyV pseudoviruses and capsomers of the main BKPyV subtypes, including when diluted in a urine matrix. The limit of detection was around 1000 ng/mL for capsomers and around 8 log10 copies/mL for culture supernatants. Antigenic detection of VP1 was compared to immunofluorescence detection of BKPyV AgT and VP1 antigens in cell cultures, and showed good correlation. Then, we obtained good results for both assays on frozen urine samples from transplant patients, previously characterized by quantitative PCR. Prospective clinical trials are currently underway to confirm these results in transplants patients and enable these assays to be implemented in routine clinical practice in the near future all around the world.
Conclusion : With these two new assays, we have the opportunity to bring a new screening and monitoring method for BKPyV in the field of transplantation with greater ease and improved biological relevance. In addition, the point-of-care test may provide easier access to BKPyV screening for low-income countries.
Professor Etienne Brochot obtained a PharmD, a postgraduate diploma in medical biology and a PhD in virology in 2010. He began his career as assistant Professor at Amiens University Hospital and Faculty of Pharmacy. Etienne Brochot was appointed Professor of Virology in 2022. Since 2015, his research has focused on the BK virus, which is posing an increasing number of problems in the context of transplants, particularly kidney transplants, and can compromise their outcome.
Antimicrobial resistance is a major problem that can affect anyone and any animals. It is crucial to limit this phenomenon in all sectors: human, animal and environment.
In order to address the problems related to antibiotic resistance, VETOPHAGE is offering a new innovative approach for both diagnostic and therapeutic solutions, based on phage proteins.
Phage is a virus that kills bacteria. They can attach to the bacteria by specific proteins which is used for the bacteria detection. The phages can produce other proteins (lysin) to destroy the bacteria wall and we can use it as an antimicrobial molecule.
Founded in 2017 by microbiology experts, VETOPHAGE owns a unique technological platform and expertize for phage protein design covering all key steps from phage biobank creation to phage protein identification and production. The phage protein receptors can be used in different approaches of immunoassays such as LFA (Lateral Flow Assays), ElISA and the conjugation with colloidal molecules. We have demonstrated the superior performance of phage proteins comparing these with different antibodies for the detection of Staphylococcus aureus. Vetophage is now commercializing the first strip tests embedding phage proteins for the detection of major pathogens causing bovine mastitis. Since 2023, Vetophage is also focusing on developing phage proteins involved in the phages’ capacity to destroy bacteria (endolysin or lysin), that could be used as novel therapeutic options for the treatment of bacterial infections. Vetophage has developed a the capacity to rapidly screen, select and optimize endolysins targeting specific bacteria. We currently have a bank of endolysins against Staphylococcus. The first chosen indication for therapeutical use is canine pyoderma.
In addition, Vetophage’s technological platform offers several specific proteins for bacterial detection and antibacterial purposes that are applicable in several fields, such as human health, animal health, or environmental microbial issues.
PhD in microbiology, after 15 years of research in the academic/private sector, expertise in phage technologies I have founded Vetophage in 2017 to use the power of phage proteins for developing innovative solutions for both diagnostic and therapeutic use
Author and co-authors of 17 publications and 6 patents on phage technologies
Antibiotic resistance, identified by the World Health Organization as a major global health threat, has prioritized the search for new therapies. Targeting the host immune response with small molecules, rather than pathogens, is a promising approach. Cochlin, a protein secreted by follicular dendritic cells, is emerging as one such candidate. Upon bacterial infections, its N-terminal LCCL domain is cleaved, released into bloodstream, and detected at the infection site.
In mouse models of bacterial lung infection, cochlin-deficient mice exhibit reduced survival associated with a diminished secretion of key pro-inflammatory cytokines (IL-1β, IL-6, TNF) and chemokines (MCP-1, KC), lower recruitment of neutrophils and macrophages to the infection site, and an increased bacterial burden. These findings suggest that the LCCL domain of cochlin plays an essential role in the protective immune response against bacterial infections even if its precise mechanism remains to be understood. Our team is focused on characterizing its mode of action as a host targeting anti-infectious agent.
In this project, through ex vivo approaches, we aimed to identify the target cells of cochlin LCCL domain and to elucidate the functional impact of its interaction with these cells.
Through flow cytometry analyses, we observed that the recombinant His-tagged LCCL domain could bind on subpopulations of different cell types (murine splenocytes, murine pneumocytes, human PBMCs) in a dose-dependent manner. We showed that this interaction was specific as no nonspecific binding was detected when His-tagged albumin was used as a control and as competition assay with non-tagged rLCCL reduced the cellular binding of His-tagged LCCL. Furthermore, though experiments with heparinase or glycosaminoglycan competitor, we showed that such binding was mediated through interaction with glycocalyx. LCCL binding was not specific to any subpopulation of leukocytes (i.e. B lymphocytes, T lymphocytes, NK cells or myeloid cells) but was detected on apoptotic and necrotic cells among those cell types. In line, we observed that mechanical or pharmacological induction of cell death (apoptosis, pyroptosis, necroptosis) in murine splenocytes enhanced rLCCL-6His binding to these cells. To assess the role of cochlin LCCL in efferocytosis (i.e. clearance of apoptotic or dying cells by phagocytes), we developed two distinct functional assays measuring the efferocytosis activity of bone-marrow-derived macrophages via confocal microscopy and flow cytometry using murine apoptotic thymocytes as target cells. In these assays, the addition of rLCCL enhanced efferocytosis, suggesting that the cochlin LCCL domain may function as an ‘eat-me’ signal, promoting efferocytosis; which strengthens its anti-infective immune response.
In total, our results show that the LCCL domain of cochlin specifically binds to apoptotic and necrotic cells across different cell types and promotes their efferocytosis by macrophages. These findings suggest that the cochlin LCCL domain may function as an ‘eat-me’ signal, enhancing clearance of dying cells and therefore contributing to the immune response.
Further understanding of the mechanisms used by molecules such as LCCL domain of cochlin may modulate efferocytosis and influence the broader immune response could open new avenues for treating infections by boosting the host’s natural defences; which is crucial in the context of rising antibiotic resistance.
I graduated as an engineer from the Ecole de Biologie Industrielle in 2021. Internships in both industrial and academic area sparked my growing interest in scientific investigation, leading me to specialize in applied research during my final two years of school and to pursue a PhD afterwards. Over the course of my four-year doctoral program, I worked on a novel immunomodulator, further developing my skills in experimental design and analysis. This experience strengthened my passion for research in the field of immunotherapies and confirmed my commitment to a career dedicated to advancing therapeutic innovations in the field of immunology.
Nanofitins are a highly modulable and hyperstable protein scaffold with great potential for treating viral pulmonary diseases and we applied this technology against influenza A virus. We developed several Nanofitin candidates efficiently neutralizing the virus and protecting infected mice via direct intranasal administration, each Nanofitin with an activity directed against a various number of subtypes. To increase the therapeutic potential of our product, we leveraged the diversity of the Nanofitin candidates identified to produce a multiparatopic and pan-specific anti-influenza A Nanofitin-based molecule, able to recognize and neutralize the different human virus subtypes. Here, we present the development of this strategy, highlighting its simplicity and its potential application to other pulmonary diseases.
Affilogic is a privately-owned biotech company specialized in discovery and development of a novel class of protein therapeutics called Nanofitins. After completing her PhD studies in Oncology and Biotherapies at the University of Nantes (France) and at Affilogic, Perrine Jacquot joined the project management team of the company in 2022. Among the different Nanofitin programs currently in development, she is focusing on the generation of Nanofitins for infectious diseases.
Membrane proteins expressed on the surface of human cells are involved in many biological processes such as the cellular immune response. These antigens are the subject of intense structural and functional studies to develop effective therapeutic antibodies. However, the production of these proteins in their native membrane state remains a difficult task due to their instability once extracted from their original membrane.
Currently, most processes involve extracting and purifying these proteins in a detergent and stabilizing them in artificial environments. These costly and time-consuming methods do not always preserve the natural oligomeric state and the complex architecture of these therapeutic targets.
Most eukaryotic cells can produce extracellular vesicles which are true intercellular communication pathways. They consist of a lipid bilayer derived from the cell’s plasma membrane and contain membrane proteins at their surface. At CytobodX, we have developed a process for rapidly obtaining native membrane proteins expressed in purified recombinant extracellular vesicles (rEVs) released by cultured mammalian cells. This technology has been validated on several classes of membrane proteins including GPCRs. The stability, functionality and integrity of proteins incorporated on rEVs have been confirmed by electron microscopy and biolayer interferometry.
We have been able to observe considerable advantages by using rEVs instead soluble protein ectodomains in terms of immunization efficiency, antigen presentation and antibody selection. This technology is definitively an advantageous tool for membrane antigen production and antibody discovery.
Vincent has been working for 20 years for many public and private research laboratories. He obtained a PhD in structural biochemistry at Aix-Marseille University in the lab “Architecture et Fonction des Macromolécules Biologiques (AFMB)”. His research focuses on the use of extracellular vesicles for the study of membrane proteins. Vincent joined the biotech CytobodX in 2021 to develop this technology dedicates to the production of membrane proteins.
Tuberculosis (TB) remains the number 1 identifiable infectious disease killer in the world. There has been a slow decline in global TB incidence and deaths over the last decade. The attenuated vaccine Bacillus Calmette-Guerin (BCG) is given to most newborns soon after birth and is excellent at preventing TB in this age group. BCG does not prevent TB in adolescents and adults, who are primarily responsible for spread of M. tuberculosis. It is widely thought that TB will not be controlled without a vaccine that effectively prevents pulmonary disease in adolescents and adults.
Progress toward the latter goal has been hampered by limited resources and an inadequate understanding of protective immunity against TB. Fourteen novel candidates are in clinical development, including 5 in phase 3 trials. The most advanced among these is the adjuvated subunit vaccine M72/AS01E-4 (Gates Medical Research Institute/GSK), which has demonstrated 49.7% efficacy in preventing pulmonary disease in a phase 2b trial involving 3,575 M. tuberculosis-infected adults (95% CI, 2.1%-74.2%). M72/AS01E-4 is now in a 20,000-person phase 3 trial.
The latest advances in TB vaccine discovery and development will be discussed, including promising preclinical candidates, efforts toward identifying host correlates of protection and global initiatives to accelerate progress.
Willem Hanekom is executive director of the Africa Health Research Institute (AHRI, www.ahri.org) in KwaZulu-Natal, South Africa. This 830-person independent academic research institute has a vision of “Optimal health and wellbeing of under-resourced populations”. He holds a professor position at University College London and affiliate professor positions at the Universities of KwaZulu-Natal, Cape Town and Washington. Willem has worked in TB vaccine discovery and development for most of his career, including directing the South African TB Vaccine Initiative (SATVI) at the University of Cape Town, and leading the TB vaccine programme at the Bill & Melinda Gates Foundation. He serves in an advisory capacity on various vaccination related committees, globally.
The COVID-19 pandemic has been a turning point for many aspects of global health and pandemic preparedness. Firstly, the pandemic accord and the related Pathogens Access and Benefit-Sharing (PABS) system will establish new rules for accessing genetic sequence information globally and for producing and distributing medical countermeasures during pandemics. Secondly, the global architecture is evolving, with greater emphasis on economic regional entities and their associated technical agencies, regulatory authorities, and research and development pathways. Thirdly, R&D is shifting towards new approaches, focusing on development platforms for families of viruses rather than individual diseases.
Dr Sylvie Briand is currently the Executive Head of the Global Preparedness Monitoring Board (GPMB) secretariat which is co-convened by the World Health Organization and the World Bank. She was previously the Director of the Epidemic and Pandemic Preparedness and Prevention department (EPP) at the World Health Organization’s (WHO) headquarters and has been at the fore front of managing epidemic and pandemic threats for more than 20 years including COVID19, avian & pandemic influenza, Ebola, Zika, MERS, yellow fever, plague, cholera, mpox, and many other emergencies of international concern.
She holds a Medical Doctor degree with a specialization in infectious diseases, a Ph.D in Health Systems’ Analysis focusing on epidemiologic surveillance, a Master’s degree in Sociology and Anthropology and a Master’s degree in Public Health.
The abstract for this presentation is currently unavailable.
Current position : Global head of Early-stage Immunology at Sanofi R&D Vaccines (Marcy-L’étoile)
Behazine Combadière, currently serving as the Global Head of Early Stage Immunology at Sanofi’s R&D Vaccines division, with significant expertise in immunology and vaccinology.
She earned her PhD in Immunology in 1993 in Paris, France, focusing her research on the regulation of HIV-specific CD8 responses. Following her PhD, she continued her research as a post-doctoral fellow at the National Institutes of Health (NIH) in Bethesda, MD, USA, from 1993 to the end of 1997. Here, she gained expertise in T cell immunity in the Laboratory of Immunology.
From 1998 to 2022, she was the Chief of laboratory at Inserm (Institut National de santé et de recherche medicale), earning several advancements over the years (from principal investigator (CR2 1998) to head laboratory (DR-1st class 2017)). She served as the Deputy Director at the Center for Immunology and Microbial Infection (Cimi-Paris) and co-directed the International Vaccinology courses at the Pasteur Institute of Paris.
She coordinated the European project EU-FP7 on HIV Vaccination from 2010 to 2016 and was a partner in the European project H2020 (EAVI2020 consortium) for the development of candidate HIV vaccines. Her research has been devoted to understanding immune mechanisms and memory in response to vaccines. She has extensive expertise in Vaccinology and immune mechanisms of action (viral diseases including smallpox, HIV, Influenza, Sars-CoV-2) and pioneered skin immunization with the development of a transcutaneous method using hair follicle targeting, which has been successful in several clinical studies. She joined Sanofi Vaccines R&D in September 2022.
She has received several awards, including the “FRM team”, the Women in Science and Innovation of ELLES – DE – FRANCE in 2020, and Chevalier de l’Ordre National du Mérite in 2022. She has a record of over 130 publications.
International Expertise in Vaccinology and Immunology
Covid International advisory Board 2021-2022
Director of International Vaccinology courses of Institute Pasteur of Paris (Paris) 2017-2022
Co-chair of Global Influenza and RSV Initiative (Singapour) – 2019-2022
Recent research into immunological memory reveals that innate immune cells can recall previous microbial encounters and exhibit modified responses, a phenomenon known as innate memory. Our work demonstrated that β-glucan from Candida albicans induces innate memory in human monocytes, enhancing immunity against unrelated pathogens. In vitro, β-glucan rapidly imprints monocytes transcriptionally, epigenetically, and metabolically within hours.
While circulating monocytes act as intermediaries before differentiating into macrophages in peripheral tissues, our findings challenge current models by showing that β-glucan does not universally enhance macrophage function and may suppress it depending on the environmental context.
Specifically, we observed that β-glucan represses IL-1β-driven inflammation, a cytokine central to inflammasome activation and autoinflammatory disorders, by modulating early activation upstream of the NLRP3 inflammasome. This insight suggests potential therapeutic applications for NLRP3-related diseases.
Finally, our in vivo studies highlight the structural specificity of β-glucan in mediating protection against fungal infections through innate immune pathways.
These findings reveal critical aspects of innate memory, paving the way for its effective clinical application.
Dr. Jessica Quintin has been the Head of the Immunology of Fungal Infection Unit at the Institut Pasteur, Paris, France, since 2015, and currently serves as Deputy Chair of the Department of Mycology. She is a board member of the Administrative Council of the French Society of Inflammation (GREMI), where she co-organized the one-day GREMI event in 2023 and will co-organize the 2025 meeting. Dr. Quintin is also a member of the Science Advisory Board for the FEBS Advanced Lecture Course on Human Fungal Pathogens, co-organized the 8th HFP in 2019, and will chair the event in 2026.
Dr. Quintin earned her PhD in Immunology studying host-pathogen interactions and has conducted extensive research on innate immune mechanisms and their applications in combating infectious diseases, with a particular focus on fungal infections. Her laboratory investigates the host immune response to human fungal pathogens such as Candida albicans and Aspergillus fumigatus, emphasizing the boundaries of immunologic memory, innate immune plasticity during secondary infections, and the diverse functions of fungal cell wall components like β-glucan.
Background:
VLA1553 is a live-attenuated chikungunya virus (CHIKV) vaccine designed for immunization against CHIKV infection for individuals travelling to or living in risk areas. With the approval of VLA1553 (brand name IXCHIQ®), Valneva’s single-dose vaccine became the first and only licensed chikungunya vaccine for use in adults aged ≥18 years.
Project description:
As chikungunya outbreaks are unpredictable and hence efficacy trials are considered unfeasible, regulators agreed to a pivotal study using a surrogate of protection as immunogenicity endpoint, later defined as μPRNT50 150 or higher, based on passive transfer studies. Therefore, VLA1553 was tested for safety and immunogenicity in healthy adults in two phase 3 trials (NCT04546724, NCT04786444).
Innovative strength & Applications:
A single dose of VLA1553 induced a rapid and strong immune response in adults (≥ 18 years), close to 100% seroresponse was achieved at Day 14, which persisted for at least 24 months. The vaccine was also confirmed to be highly immunogenic in older adults (≥ 65 years). Additionally, VLA1553 elicited immunity efficiently neutralized all three major CHIKV genotypes.
In terms of safety, VLA1553 was generally well tolerated across all age groups.
Conclusion:
The ongoing pediatric clinical development of VLA1553 aims to expand its availability across all age groups.
Keywords:
chikungunya, clinical development VLA1553, vaccine IXCHIQ®
Martina Schneider holds a PhD in virology and is a registered nurse with a robust medical background. She has been working as a Clinical Strategy Manager at Valneva, a French biotech company specializing in vaccines for infectious diseases with significant unmet medical needs, for the past five years. In her role, Martina has been instrumental in leading the pivotal Phase 3 trial for the chikungunya vaccine candidate VLA1553, that has been published in Lancet.
The abstract for this presentation is currently unavailable.
I joined the VirPath laboratory in 2012 for Master internship and then, pursued my academic education with a thesis in international cotutelle program between LVMC team (Université Laval/CHU de Québec, Canada) and Virpath team (Université Claude Bernard Lyon1, France). During thesis (2014-2018), I worked on Human Metapneumovirus (HMPV) virulence factors and I developed a live-attenuated vaccine platform against HMPV, the Metavac vaccine platform. After thesis, I co-founded the Vaxxel start-up and worked as Research & Development Project Manager from 2020 to 2023 to develop vaccine-candidates against HMPV and Respiratory Syncytial Viruses (RSV) based on the versatile Metavac® vaccine platform. In 2023, I reintegrated the Virpath laboratory as associate scientist researcher to develop and participate in other vaccine-oriented research programs to understand and better control human infection by respiratory viruses (HMPV, RSV, Influenza and SARS-CoV).
The Blue Tongue Virus (BTV) is the causative agent of a severe seasonal transboundary diseases affecting ruminants. The recent BTV serotype 3 (BTV3) outbreak, rapidly spreading through Europe, has a significant impact on animal health and is causing severe losses for farmers. In the absence of cross-protection by existing vaccines, a BTV3 vaccine was required.
Since the identification around 2018 of the BTV3 threat at EU borders, BIAH had anticipated the production of a BTV3 master seed virus. Following the outbreak in Sep 2023, this strain entered quickly in development on an existing vaccine platform to respond to the emergency. This new vaccine has been industrialized for mass production and tested to confirm efficacy against the currently circulating BTV3 strain. This new unauthorized vaccine got exceptional allowance of use in multiple European countries, based on the Art.110 of EU Regulation 2019/6 for emergency.
Thanks to our preparedness, and reactivity in vaccine development, thanks to the EU regulation designed to act in such emergency situation, thanks to the willingness of Governments and farmers to use this emergency vaccine and protect their herds, vaccination took place over the 2024 summer, and BTV3 virus negative impacts on animal health and on economic losses were significantly reduced.
I’m a PhD in Cancer Biology by training. I first worked in Human diagnosis and joined Animal Health 15 years ago at Merial and now BI, dedicated to Veterinary Public Health. I lead R&D projects to develop and register vaccines and to make them available for commercialization to prevent emerging & transboundary animal diseases such as Bluetongue, Foot and Mouth Disease and other notifiable diseases. In particular, I’m in charge of updating the strain portfolio to adapt our vaccines to the epidemiology and to the regular emergence of new variants of these diseases.
The concurrent rise of antimicrobial resistance and incidence of sexually-transmitted infections is a worrying combination. In the past decade, cases of gonorrhoea have more than doubled in many countries – in the US for example this means more than 1.6 million new infections last year, half of which were antibiotic resistant.
The effectiveness of vaccines in the fight against AMR has already been demonstrated. Widespread introduction of the pneumococcal conjugate vaccine led to a dramatic reduction in antibiotic usage, and even reduced levels of resistance among circulating strains. Thus, we are convinced of the power of vaccination as a strategy.
LimmaTech Biologics is developing a vaccine against N. gonorrhoeae based on multiple conserved, novel antigens. Our approach is designed to overcome the natural immune evasion and suppression mechanisms of N. gonorrhoeae. We have generated preclinical data confirming the immunogenicity of our vaccine as well as confirming bactericidal activity of the resulting antibodies. GMP production is ongoing and we plan to begin clinical testing in 2026.
Michael is Chief Scientific Officer of LimmaTech and responsible for the scientific development, pipeline expansion and operational R&D performance. He has a PhD in Biochemistry from the Swiss Federal Institute of Technology, Zurich (ETH Zurich) and has developed broad experience in the biotech industry. After university, he joined GlycoVaxyn to develop the company’s bioconjugation vaccine platform. He ran a collaboration that culminated in GlycoVaxyn’s acquisition by GlaxoSmithKline in February 2015 after which Michael became a co-founder of LimmaTech, and took the role of VP of Business Strategy and IP to drive the proprietary company business, marking his journey into therapeutics. With the successful spin-out of the therapeutics assets into the newly formed company GlycoEra AG in January 2021, he became CSO Vaccines of LimmaTech, moving back to his true scientific passion, developing innovative vaccines.
The World Health Organization (WHO) lists AMR among the top 10 threats for global health. By 2050, up to 10 million deaths could occur annually due to some type of infection caused by a pathogen carrying antimicrobial resistance mechanisms, according to recent estimates. NG Biotech will be presenting how its innovative, rapid, multiplex diagnostic tools contribute to identify and characterize at an early diagnostic workflow stage Carbapenemase-Resistance, ESBL-Resistance and in addition Colistin-Resistance, supporting adequate, precise, current and novel antibiotics selection and helping clinicians worldwide in over 80 countries combat the spread of Antimicrobial Resistance and implement robust antimicrobial stewardship programs.
Milovan, currently CEO of NG Biotech, founded the company with other industry leading partners in 2012 to develop diagnostic solutions for the problem of Antimicrobial Resistance (AMR). Over the past 10 years, the company has developed and introduced to the global clinical microbiology market a leading range of Rapid Tests for the reliable, precise detection and identification of the mechanisms of Antimicrobial Resistance, contributing to the advance of targeted antibiotic therapies, reduction in the overuse of large-spectrum antibiotic, conserving the efficacy of last-line antibiotics and saving countless patient lives. Today the NG-Test CARBA-5 (Carbapenemase-Resistance detection+identification), is the world number 1 AMR Rapid Test, with more that 1 million units per year being registered and commercialized in over 80 countries and reaching all continents.
Since 2017, we have attempted to demonstrate the value of assessing immune function through the use of Immune Functional Assays (IFAs), both antigen-specific and non-specific mitogenic, in various clinical contexts. Thanks to the antigen-specific approach, we have demonstrated that IFAs appear to be a suitable and rapid option for assessing the presence of long-term specific cell-mediated immunity, with an interest in establishing reliable correlates of protection (CoP) and optimizing vaccine and therapeutic prophylaxis on a case-by-case basis. Using a non-specific approach, we also highlighted the ability of transcriptomic IFAs to reveal functional immune alterations and to track their temporal evolution within an immunocompromised population of allo-HSCT recipients.
After three years as a laboratory technician, I joined the HCL in late 2014, working within the Staphylococcus Pathogenesis team at CIRI under the supervision of Prof. F. Laurent. During my four years with the team, I resumed my studies and earned a Master’s equivalent in December 2018 from the École Pratique des Hautes Études.
In January 2019, I joined bioMérieux in the HCL-bioMérieux Joint Research Unit, where I pursued a CIFRE PhD under Dr. S. Trouillet-Assant. My research focused the functional alterations in the immune system of immunocompromised individuals. Since June 2022, I have returned to HCL within the same Joint Research Unit as a postdoctoral researcher, still focusing on functional immune responses in various clinical contexts and co-supervising a PhD student.
