Publications
Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleRosenheim J, Bender B, Gilmour J, et al., 2026,
Conference report: airway mucosal sampling and immune analysis.
, Vaccine, Vol: 88Respiratory pathogens cause substantial global morbidity, mortality, and pandemic risk. While parenteral vaccines can effectively reduce severe disease for some respiratory infections, they are often less effective at preventing infection and onward transmission. Vaccines delivered directly to the airways have the potential to induce protective mucosal immunity at the site of pathogen entry. However, progress in mucosal vaccine development has been constrained by limited understanding of airway immune mechanisms, the technical challenges of sampling respiratory tissues, and the lack of standardised, validated immunological assays capable of defining mucosal correlates of protection. To address these challenges, the Novo Nordisk Foundation and Wellcome Trust convened a workshop on airway mucosal sampling and immunological assays, bringing together researchers, clinicians, funders, and representatives from major research consortia. Participants reviewed approaches to sampling the upper and lower respiratory tract, assay technologies, and regulatory considerations for integrating mucosal endpoints into vaccine development. Discussions highlighted major barriers including variability in sampling techniques, low and inconsistent cell yields, limited assay standardisation, and insufficient cross-study comparability. The workshop produced a set of recommendations in four priority areas (i.e., Collaboration, Communication, Consistency and Conduct of research) to share knowledge, accelerate standardisation and validation, and generate evidence supporting mucosal vaccine development. Together, these advances will help strengthen the scientific and regulatory foundations needed to realize the full potential of airway-delivered vaccines for the prevention of respiratory diseases.
-
Journal articleDvorscek AR, Kushnir AS, Dibben O, et al., 2026,
Mucosal immunity as a vaccine-induced correlate of protection against influenza.
, Mucosal ImmunolLicensure of influenza vaccines relies on serum hemagglutination inhibition (HAI) titers, a correlate of protection (CoP) that was developed more than 50 years ago and which is only poorly predictive of protection. This is especially true of immunity induced by intranasal live attenuated influenza vaccines (LAIVs). Unlike intramuscular inactivated influenza vaccines (IIVs), LAIV and natural infection selectively stimulate mucosal immunity. Developments in mucosal immunology now enable measurement of diverse aspects of mucosal immunity, including the frequencies and functions of nasal antibodies, T cells, and B cells. This review assesses the potential of new sampling and assay approaches that may overcome inconsistent findings from previous methodologies. Standardization of the collection and assessment of mucosal samples is essential in developing new CoPs for vaccine development and licensure of novel vaccines that induce nasal protection and are more effective in prevention of viral transmission.
-
Journal articleDavies JC, Bakkeheim E, Chansard A, et al., 2026,
Perspective of the European Cystic Fibrosis Society on Improving Global Cystic Fibrosis Care.
, Pediatr Pulmonol, Vol: 61INTRODUCTION: Outcomes for people with the inherited disease, cystic fibrosis, have improved greatly over the last few decades, but one result of this is a widening gap between regions with high income and well-resourced healthcare systems and low/middle income countries. The gap stretches from newborn screening programs, provision of standard diagnostics and genetic testing through to access to standard of care therapies. METHODS AND RESULTS: This paper describes the various initiatives of the European Cystic Fibrosis Society: our Patient Registry, a Twinning Program linking centers from different regions and our Educational Program. CONCLUSIONS: The European Cystic Fibrosis Society recognizes this as a major issue and seeks through these programs to support colleagues, patients and families in low/middle income countries.
-
Journal articleBell RV, Faulkner NB, Sinadinos A, et al., 2026,
Assessment of F/HN-pseudotyped lentiviral vector following intravenous delivery to mice.
, Gene TherIn pursuit of a gene transfer agent with efficient pulmonary transduction, the UK Respiratory Gene Therapy Consortium has developed a lentiviral vector pseudotyped with the envelope proteins, F and HN from Sendai virus (rSIV.F/HN). In contrast to other viral vectors, pulmonary rSIV.F/HN delivery achieves sustained gene expression ( ~ 2 years in mice) in the lungs and systemic circulation following a single dose. Here, we investigate the application of the rSIV.F/HN vector-platform for wider indications, including systemic disorders that require serum expression of therapeutic proteins. To assess the potential for rSIV.F/HN to produce systemic proteins, intravenous vector delivery was characterised and compared against intrapulmonary administration, achieved via 'nasal sniffing'. Both delivery routes achieved sustained (at least 1 year) systemic expression of the secreted reporter protein Gaussia luciferase. Systemic rSIV.F/HN delivery resulted in widespread protein expression across multiple organs, accompanied by the generation of significant anti-vector neutralising antibodies limiting vector readministration. Conversely, localised airway transduction was observed following pulmonary administration, which we have previously shown is not an impediment to efficient vector readministration. These data support intrapulmonary rSIV.F/HN delivery for systemic protein production, with sustained high-level transgene expression and feasible readministration.
-
Journal articleSinadinos A, Bell R, Juarez-Molina CI, et al., 2026,
Using the nose as a factory to secrete proteins into the lungs or circulation
, Molecular Therapy Advances, Vol: 34, ISSN: 3117-387XTargeting of the nasal epithelium for sustained therapeutic protein secretion represents a potential non-invasive lentiviral vector application strategy. Using reporter imaging, molecular, and radiopharmaceutical tracing methods in mice, we have developed an intranasal (nose-only) dosing strategy with a Sendai-virus envelope glycoprotein pseudotyped lentiviral vector (rSIV.F/HN). Using multiple (up to 10) small volume (5 μL) intranasal bolus applications, technetium radiotracer showed >90% liquid retention in the murine head and <1% in the lung. Following vector administration, transgene expression was dose-related in the nose with minimal lung expression. No acute nasal toxicity was associated with nose-only delivery. Next, we compared levels of a secreted protein, Gaussia luciferase (Gluc), in the airways and serum after nose-only and intravenous administration of rSIV.F/HN-Gluc (2e8 TU/mouse). Gluc expression in the nose and lungs was higher following nose-only versus intravenous administration. Serum levels were similar after either route of administration. Finally, nose-only delivery of rSIV.F/HN encoding GM-CSF, led to sufficient lung levels of this therapeutic protein to correct disease biomarkers in a mouse model of pulmonary alveolar proteinosis. We conclude that non-invasive administration of a lentiviral vector to the nasal epithelium provides a safe and convenient route for secreted protein production and is readily translatable into humans.
-
Journal articleShort C, Semple T, Abkir M, et al., 2026,
Oxygen-enhanced MRI and multiple breath washout with Short extension reveal cystic fibrosis lung disease progression despite triple modulator therapy.
, ThoraxINTRODUCTION: The current cystic fibrosis (CF) care era, while hugely welcome, raises new challenges, particularly the need for more sensitive pulmonary outcome measures. Seeking further optimisation, we previously developed a Short extension to multiple breath washout measure (MBWShX) which captures previously overlooked, under-ventilated lung units but lacks regional information. Functional lung MRI addresses this limitation. We hypothesised these measures would be more sensitive to change in tracking CF lung disease than usual clinical respiratory function tests. METHODS: Forty-six people with (pw)CF, median age 15 (range 6-55) years were recruited to a single-centre study. While clinically stable, pwCF performed OE-MRI, MBW+/-ShX and spirometry at baseline and at 6 monthly intervals over 18 months of follow-up. A subgroup of pwCF (n=20) and age-matched healthy controls (HC, n=20) performed two repeatability visits within 6 weeks. RESULTS: OE-MRI/MBWShX were well tolerated, differentiated HC and CF groups, and were repeatable with negligible differences between two visits <6 weeks apart. OE-MRI/MBWShX parameters worsened at 12 months (p<0.05) and 18 months (p<0.01). In contrast, conventional measures of pulmonary function (FEV1+ LCI2.5) did not change significantly. CONCLUSIONS: OE-MRI/MBWShX are novel, sensitive tools to track progression of abnormalities in lung structure/function. Such progression may not be detected by conventional outcome measures. CF transmembrane conductance regulator (CFTR) modulators have been transformative for many pwCF and generally lead to substantial improvements in lung health. Stable FEV1 over longer time periods and, during mucoactive treatment withdrawal, may give false reassurance. OE-MRI/MBWShX reveal the likely less welcome reality that lung-disease progresses despite CFTR modulators. These measures could be considered in future studies when enhanced sensitivity is required.
-
Journal articleHarker JA, Thwaites RS, 2026,
Restoring β2AR responsiveness in neonatal RSV.
, Am J Respir Crit Care Med, Vol: 212, Pages: 1189-1191 -
Journal articleDavies JC, Wilson G, Hughes D, 2026,
Variability: the law of life?
, Thorax, Vol: 81, Pages: 511-513 -
Journal articleDe Boeck K, Burgel P-R, Bierlaagh M, et al., 2026,
ECFS statement on theratyping and theranostics in the context of rare and ultrarare CFTR variants in people with CF.
, J Cyst FibrosGenotype-based drug development has yielded highly effective therapies, notably the triple combinations elexacaftor/tezacaftor/ivacaftor (ETI) and vanzacaftor/tezacaftor/deutivacaftor (VTD), now approved in Europe for people with CF having at least one non-class I variant. However not all these people with CF will respond to ETI or VTD, and a few not under the label may respond. Facilitating opportunities to access for patients with rare variants has required a shift in paradigm toward functional testing-based access. This approach assesses the potential benefit of modulator therapy using in vitro functional assays, either in engineered systems expressing defined CFTR variants (theratyping) or in patient-derived tissues (theranostics). We review theranostics as a critical tool for personalized medicine in CF, highlighting its validation in in vitro models derived from patients' own cells such as human intestinal organoids and human nasal epithelial cells. We discuss the current regulatory landscape regarding modulator approval and propose strategies for improving equitable access to effective treatments for all people with CF. Importantly, we advocate for functional assays to be accepted as standalone evidence of drug efficacy for patients with rare variants. Theranostic approaches remain critical when theratyping has not been achieved, and genetic data is not available or clearly interpretable. Indeed, theranostics has emerged as an essential pillar of CF drug access, complementing genotype-driven strategies. As the field advances, continued validation, standardization, and regulatory integration of in vitro functional assays will be key to ensuring that every person with CF-regardless of their genotype-has the opportunity to benefit from precision therapies.
-
Journal articleFarias A, Bridgeman VL, Rodrigues FS, et al., 2026,
Type I interferons induced upon respiratory viral infection impair lung metastatic initiation.
, Proc Natl Acad Sci U S A, Vol: 123Metastatic breast cancer accounts for 7% of cancer-related deaths, with the lungs being a common site of cancer spread. In parallel, lower respiratory tract infections, including those caused by respiratory syncytial virus (RSV), remain a common cause of morbidity and mortality worldwide. Acute viral respiratory infections induce marked changes in the lung. However, how these changes influence metastasis initiation and cancer progression remains unclear. Using breast cancer and other cancer cell types in an experimental lung metastasis model, we show that RSV infection impairs tumor cell seeding and early growth in the lung, resulting in fewer metastatic nodules. We demonstrate that restriction of metastatic spread is due to alterations in the lung environment mediated by RSV-induced type I interferons (IFNs). Consistent with this idea, intranasal administration of recombinant IFN-α is sufficient to recapitulate the anti-metastatic effect of RSV infection. Using single cell RNA sequencing supported by in vivo and ex vivo validation, we show that IFN-α influences interactions between epithelial/endothelial cells and cancer cells. Furthermore, both RSV infection and IFN-α administration trigger marked local and systemic upregulation of Galectin-9, an IFN-inducible protein associated with acute respiratory infection in humans. Treatment of cancer cells with Galectin-9 alone is sufficient to restrict metastatic seeding. Altogether, our results suggest that type I IFNs induced by respiratory virus infection render the lungs less permissive to cancer cell seeding and consequently interfere with the ability of tumor cells to successfully initiate metastatic colonization.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.