Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are the main etiologic agents of viral bronchiolitis and pneumonia in children and the elderly. As live-attenuated vaccines (LAV) can stimulate robust mucosal and cellular responses, we previously engineered an HMPV-based bivalent LAV Metavac®-RSV candidate and reported its capacity to protect mice against HMPV and RSV challenges after intranasal delivery. To progress towards clinical development, we identified a GMP-grade Vero cell platform as permissive and efficient to produce high yields of functional Metavac®-RSV, expressing both RSV and HMPV F antigen after several passages.
View Article and Find Full Text PDFJ Crohns Colitis
July 2025
Background And Aims: Pneumococcal vaccination is essential for patients with inflammatory bowel diseases (IBD), but its efficacy is reduced in those on antitumor necrosis factor (TNF) or immunosuppressive therapy. This study compared immune responses to standard versus intensified pneumococcal vaccination strategies in IBD patients receiving anti-TNF (±immunosuppressors) or vedolizumab.
Methods: In a prospective, multicenter, randomized open-label study across 7 French university hospitals, IBD patients in clinical remission on biologic therapy (anti-TNF ± immunosuppressors, or vedolizumab) were randomized 1:1 to an intensified (PCV13/PCV13/PPSV23) or standard (PCV13/PPSV23) regimen.
System serology offers a comprehensive approach to evaluate the humoral immune response by evaluating multiple parameters. In the present study, based on four groups of individuals with a different history of SARS-CoV-2 immunization, we analyzed the serum of 180 individuals based on six serological methods to better decipher their immunity. Through our analysis, against different SARS-CoV-2 antigens or variants, we report the importance of system serology to better decipher population immunity.
View Article and Find Full Text PDFBackground: In France, a standardized procedure has been introduced in which 5 units of plasma derived from whole blood are pooled into two equal volumes for pathogen reduction treatment (PRT). This method produces 6 fresh frozen plasmas treated with Amotosalen and Ultraviolet A (UVA) (FFP-A/UVA) from 5 native plasmas, reducing treatment time and disposable set costs, standardizing products, and decreasing adverse events by diluting allergens, cytokines, and antibodies.
Materials And Methods: This study aimed i) to compare concentrations of Factor VIII, fibrinogen, and soluble inflammatory factors in ABO-isogroup or universal plasma pools with or without A/UVA PRT, and ii) to evaluate the profile and standardization of plasma units in mini-pools (5 units) and maxi-pools (10 units).
As professional and long-lived immunoglobulin (Ig) producers, B cells represent attractive candidates for adoptive immunotherapy and their highly expressed Ig heavy (IgH) chain locus is ideal for editing. Each of its constant genes, expressed after class switch recombination (CSR), affords an attractive platform where an adoptive Ig variable domain would acquire IgM, IgG, IgE or IgA class-specific functions. In particular, IgA plays a unique role in mucosal immunity but has remained excluded from therapeutic applicability due to unfavorable chemistry, manufacturing, and control (CMC) issues.
View Article and Find Full Text PDFIntroduction: The clinical efficacy of Janus kinase inhibitors (JAKinibs) is highly variable and their safety profiles are poorly understood.
Methods: We established two flow cytometry panels for the assessment of two promising leukocyte biomarkers: signal transducer and activator of transcription (STAT) phosphorylation and cytokine receptor expression. We evaluated the first panel, which assesses phosphorylation levels for STAT1, STAT3, and STAT5 after cytokine stimulation, with or without pretreatment with JAKinibs, in 10 healthy donors.
The effectiveness of intramuscular vaccines aimed at preventing severe COVID-19 remains limited due to waning immunity and the emergence of novel variants. Next-generation vaccines are needed for broader protection and blocking virus transmission. Here, we rationally designed an original nasal subunit vaccine composed of a fusion protein (SwFN) made of Wuhan spike and nucleoprotein combined with biocompatible mucosal nanocarriers (Nc).
View Article and Find Full Text PDFImmune memory is influenced by the frequency and type of antigenic challenges. Here, we performed a cross-sectional comparison of immune parameters following a BA.1 breakthrough infection in individuals with prior hybrid immunity (conferred by infection and vaccination) versus those solely vaccinated in a cohort of health care workers in Lyon, France.
View Article and Find Full Text PDFJ Peripher Nerv Syst
March 2025
Background And Aims: Immune-mediated sensory neuronopathies (SNN) can occur alongside autoimmune disorders (e.g., Sjögren syndrome), involve autoantibodies (such as anti-FGFR3 or anti-AGO antibodies), or present in isolation.
View Article and Find Full Text PDFSensory neuronopathies (SNN) encompass diverse etiologies, with autoimmunity playing a major role through both cellular and humoral responses. To investigate the humoral autoantibody repertoire in autoimmune SNN, we conducted a retrospective cohort study using large Human Proteome-wide protein microarrays (HuProt 3.1, HuProt 4.
View Article and Find Full Text PDFAvolition is a symptom responsible for a high burden in patients suffering from psychiatric diseases. It refers to a motivation loss for initiating and maintaining goal-directed activities, often called fatigue by patients. Fatigue is a widespread complaint of patients suffering from inflammatory bowel disease (IBD), significantly impacting patients' well-being, even during the quiescent stage of the disease.
View Article and Find Full Text PDFExpert Rev Gastroenterol Hepatol
October 2024
Emerg Microbes Infect
December 2024
Several studies have investigated the antibody response to SARS-CoV-2, focusing particularly on the systemic humoral immune response and the production of immunoglobulin G (IgG) antibodies. IgA antibodies play a crucial role in protecting against respiratory viral infections but have also been associated with the pathophysiology of COVID-19. We performed a prospective study of 169 COVID-19 patients - 50 with critical/severe (ICU), 47 with moderate (Non-ICU), and 72 with asymptomatic COVID-19 - to explore the humoral immune response to SARS-CoV-2 infection.
View Article and Find Full Text PDFIn the human and veterinary fields, oral vaccines generate considerable interest. In dogs, these vaccines are newly developed, and understanding their mechanisms is crucial. Mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) are important sites for gastrointestinal mucosal induction, yet canine MLNs lack sufficient information.
View Article and Find Full Text PDFClin Microbiol Rev
September 2024
SUMMARYHealthcare-associated infections (HAIs) represent a burden for public health with a high prevalence and high death rates associated with them. Pathogens with a high potential for antimicrobial resistance, such as ESKAPE pathogens ( and ) and , are responsible for most HAIs. Despite the implementation of infection prevention and control intervention, globally, HAIs prevalence is stable and they are mainly due to endogenous pathogens.
View Article and Find Full Text PDFCoordinating immune responses - humoral and cellular - is vital for protection against severe Covid-19. Our study evaluates a multicytokine CD4T cell signature's predictive for post-vaccinal serological and CD8T cell responses. A cytokine signature composed of four cytokines (IL-2, TNF-α, IP10, IL-9) excluding IFN-γ, and generated through machine learning, effectively predicted the CD8T cell response following mRNA-1273 or BNT162b2 vaccine administration.
View Article and Find Full Text PDFInflamm Bowel Dis
February 2025
Background: There are limited data regarding therapeutic drug monitoring (TDM) of non-anti-tumor necrosis factor therapy in inflammatory bowel disease (IBD). This study aimed to evaluate the efficacy of proactive TDM in IBD patients treated with intravenous (iv) vedolizumab (VDZ).
Methods: This single-center retrospective cohort study included consecutive IBD patients treated with maintenance iv VDZ therapy undergoing TDM from November 2016 to March 2023.
Live-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV), the main etiologic agents of viral bronchiolitis and pneumonia in children. We inserted the RSV-F gene into an HMPV-based LAV (Metavac®) we previously validated for the protection of mice against HMPV challenge, and rescued a replicative recombinant virus (Metavac®-RSV), exposing both RSV- and HMPV-F proteins at the virion surface and expressing them in reconstructed human airway epithelium models. When administered to BALB/c mice by the intranasal route, bivalent Metavac®-RSV demonstrated its capacity to replicate with reduced lung inflammatory score and to protect against both RSV and lethal HMPV challenges in vaccinated mice while inducing strong IgG and broad RSV and HMPV neutralizing antibody responses.
View Article and Find Full Text PDFAcute, transient lymphocytopenia, not clinically significant was observed in the CAPRISA 012B phase 1 clinical trial following administration of broadly neutralizing antibodies (bnAb)-CAP256V2LS alone or with VRC07-523LS. Lymphocytopenia was assigned upon a > 50% decline in absolute lymphocyte counts following bnAb administration. We posited that systemic immunoglobulins (Igs), and cytokine profiles of eight women who developed lymphocytopenia were different to the 12 women without lymphocytopenia.
View Article and Find Full Text PDFLinks between the gut microbiota and human health have been supported throughout numerous studies, such as the development of neurological disease disorders. This link is referred to as the "microbiota-gut-brain axis" and is the focus of an emerging field of research. Microbial-derived metabolites and gut and neuro-immunological metabolites regulate this axis in health and many diseases.
View Article and Find Full Text PDFRisankizumab (RZB) is a monoclonal antibody that targets the p19 subunit of interleukin (IL)-23. The ADVANCE and MOTIVATE randomized controlled trials (RCTs) demonstrated that intravenous (IV) RZB compared with placebo led to higher rates of clinical remission and endoscopic response at week 12 in patients with active Crohn's disease (CD). The phase III FORTIFY RCT showed that subcutaneous (SC) RZB was significantly more effective than placebo for achieving clinical remission and endoscopic response as maintenance therapy in patients with moderate-to-severe active CD.
View Article and Find Full Text PDFImportance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response.
Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection.
Design, Setting, And Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France.