Can a woman with an optimal vaginal microbe donate and thereby resolve molecular vaginal dysbiosis in another woman???
We wanted to answer the question in this first randomised controlled trial - It was one of the studies in Tine WrĂžnding PhD - she organised more than 900 clinical visits to make this possible and it has been a remarkable team effort - huge thanks to everybody involvedđȘđ
Although some women experienced donor microbiome engraftment - especially after pre-treatment - and although we learned a lot about the vaginal microbiome - this is a negative trial - going forward we need to explore who will benefit vaginal microbiome transplantation or find alternative ways to treat vaginal dysbiosis đŹ
It appeared less than 40 years ago, while systemic immunity exploded 60Â years ago.
It is still a minor part of Immunology teaching and research, while the mucosal immune system is at the frontline of encounters with germs, antigens... in other words the environment.
2ïžâŁ 0ïžâŁ years ago, a #microbiota analysis of samples from patients with #Crohn's disease turned up something consistent: one bacterium was missing in patients who relapsed, who progressed to surgery, who failed biologics. #Faecalibacterium prausnitzii. And this bacterium exhibited anti-inflammatory effects in vitro and in mice!
What followed was two decades of mechanistic work: â MAM protein blocking NF-ÎșB (https://lnkd.in/eWa9rU6P) â CD4+CD8αα+ regulatory T cells specific for F. prausnitzii (https://lnkd.in/e5EUCAXY), â and CD14+ monocytes rewired toward anti-inflammatory energy metabolism (https://lnkd.in/eREPZy93).
By 2016, that body of evidence was strong enough to build a company. Exeliom Biosciences was founded that year to turn the science into a drug (https://lnkd.in/efAgpyT9).
â¶ïž The MAINTAIN study is where that bet was tested in humans for the first time.
đŠ After induction with corticosteroids, eight patients with mild-to-moderate Crohn's disease received oral EXL01 (10Âčâ° bacteria/day) for up to 24 weeks. No treatment-related adverse events. EXL01 was recovered in up to 42.8% of stool samples during treatment.
𧏠Ileal transcriptomics detected upregulation of energy metabolism and mucosal immune pathways, without broad compositional shifts in the microbiome. The bacterium acts on host cells directly, not by remodeling the community. The two patients who flared showed markedly higher CRP and platelets at baseline. Before EXL01 was started, suggesting that the corticoid treatment did not work for them.
A phase 2 randomized controlled trial is ongoing to evaluate the effect of EXL01 in preventing postoperative recurrence in CD (NCT06925061) with Groupe REMIND
With Perle Guarino-Vignon, Edouard Louis, Hang Phuong PHAM, Geert DHaens, Philippe Langella, Nathalie Rolhion and all co-authors.
As Prof Robert Clancy explains, itâs not just about fighting pathogens - itâs about understanding the đŻđźđčđźđ»đ°đČ⊠the đđ¶đ» đźđ»đ± đđźđ»đŽ of our immune system.
And when that understanding is absent? Decisions are made from an incomplete picture.
During COVID, we saw this play out - authoritative voices speaking with certainty⊠yet lacking foundational knowledge in this space.
Thatâs not just a gap. Thatâs a risk to public health.
This conversation isnât about criticism - itâs about evolution.
Medicine must move forward. And that starts with asking better questions.
Whatâs your take - should immunology be rethought in modern medicine?
Can a woman with an optimal vaginal microbe donate and thereby resolve molecular vaginal dysbiosis in another woman???
We wanted to answer the question in this first randomised controlled trial - It was one of the studies in Tine WrĂžnding PhD - she organised more than 900 clinical visits to make this possible and it has been a remarkable team effort - huge thanks to everybody involvedđȘđ
Although some women experienced donor microbiome engraftment - especially after pre-treatment - and although we learned a lot about the vaginal microbiome - this is a negative trial - going forward we need to explore who will benefit vaginal microbiome transplantation or find alternative ways to treat vaginal dysbiosis đŹ
Most pathogens donât wait for an invitation, they enter through our mucosal surfaces.
A recent paper in Nature Reviews Immunology highlights a critical gap in how we think about vaccines: while traditional injected vaccines are excellent at preventing severe disease, they often fall short at the bodyâs frontlines; the respiratory, gastrointestinal, and urogenital mucosa.
đŹ Key takeaway: To truly control infections (and not just reduce symptoms), we need to design vaccines that generate strong mucosal immunity.
Hereâs why this matters:
âą Mucosal tissues are the first point of contact for most pathogens âą Local immune defenses (like IgA and tissue-resident memory cells) can stop infections before they start âą Current systemic vaccines donât always induce strong protection at these sites âą Mucosal vaccines (e.g., nasal or oral) could help block transmission, not just disease
đĄ The future of vaccination may lie in integrated strategies: Systemic priming + mucosal boosting = broader, more effective protection
This shift is especially relevant for respiratory and emerging zoonotic diseases, where stopping transmission is just as important as treating illness.
As we continue to rethink vaccine design, one thing is clear; the protection at the entry point could change the game.
đ«Â Uncovering the Lungâs Local Immune Network
When a virus enters the lungs, the immune system must respond immediately. The King lab, Jean de Lima as first author, at the Department of Biomedicine and the UniversitĂ€t Basel has now identified a specialized group of CD4âș T cells that coordinate a local immune defense directly within the lung.
These T cells produce a molecule called HIF-1α, which is typically known as a cellular stress sensor but can also be activated by immune signals. Using advanced imaging methods, the team mapped how these cells position themselves at the outer edges of small immune hubs and release interleukin-21 (IL-21) to activate neighboring cells. When HIF-1α was switched off in the T cells, the local immune network collapsed, leaving the lungs poorly equipped to fight off a second infection with a different influenza strain.
The same HIF-1α-driven T cells were also found in a mouse model of lung cancer, where they supported the immune systemâs fight against tumor cells. This suggests that the lung maintains its own immune ecosystem â a coordinated community of cells with distinct roles in tissue defense.Â
This discovery provides important insight for developing inhalable mucosal vaccines that protect the lungs where viruses first enter, and it may also inform new strategies for tissue-targeted immunotherapies.
𧏠Programming lung immunity through mucosal vaccination
A new Science Magazine study shows how intranasal vaccination can induce broad protection against diverse respiratory threats in mice.
Using an intranasal liposomal formulation combining TLR4 and TLR7/8 agonists with antigen, the authors demonstrate durable protection against multiple viral and bacterial respiratory infections, as well as allergic airway inflammation.
Multi-omic profiling of lung tissue reveals several key features of this response:
đč Durable tissue-resident T cell immunity Intranasal vaccination induces persistent antigen-specific CD4âș and CD8âș tissue-resident memory T cells (TRM) in the lung that remain detectable for months.
đč Epigenetic reprogramming of alveolar macrophages Single-cell transcriptomic and chromatin accessibility analyses reveal sustained transcriptional and epigenomic remodeling of alveolar macrophages, enhancing antigen presentation, phagocytosis, and antiviral responses.
đč T cellâinnate cell cross-talk via RANKL signaling Memory T cells imprint macrophage function through RANKL-mediated signaling, establishing a feed-forward circuit between adaptive and innate immunity within lung tissue.
đč Rapid spatial immune organization upon infection Following challenge, vaccinated lungs rapidly form tertiary lymphoid structures, enabling accelerated pathogen-specific T- and B-cell responses.
These findings support the concept of âintegrated organ immunityâ - a coordinated network of tissue-resident immune and structural cells that can provide broad protection against diverse respiratory threats.
đĄ The study also highlights how integrating spatial transcriptomics, single-cell RNA-seq, and chromatin accessibility profiling enables detailed mapping of immune programming directly within lung tissue microenvironments.
đ Zhang et al., Science (2026) Mucosal vaccination in mice provides protection from diverse respiratory threats
Glycans are essential components of homeostatic networks, acting as fine tuners of immunological responses, and are therefore promising targets for manipulating immune tolerance. Glycans shield the entire gut mucosa surface, contributing to epithelial barrier integrity. Moreover, most microorganisms expose glycoconjugates on their surfaces, making glycans essential molecules in the crosstalk between host immune response and the gut microbiota. The vast amount of biological information encoded by mucosal glycans is deciphered by a variety of glycan-binding proteins that translate glycan recognition into either pro-inflammatory or anti-inflammatory responses. Current evidence from inflammatory bowel disease (IBD) has highlighted the prominent role of glycans in establishing and regulating key cellular and molecular pathways underlying the transition from health to intestinal inflammation, with implications for understanding IBD immunopathogenesis and for IBD prediction and prevention. In this Review, we discuss current advances, emerging challenges and future prospects in exploiting the power of the mucosal glycocalyx and the glycome as master coordinators of the immunoregulatory networks in IBD from the preclinical phase to established diagnosis. We discuss the clinical utility of the glycome as a serological biomarker with diagnostic, prognostic and predictive value, and as a potential new target for preventive intervention strategies in IBD. Glycans are essential components of the gut mucosa that modulate epithelial barrier integrity, hostâmicrobiota interactions and gut immune response. This Review discusses the role of mucosal glycans in gut homeostasis, in intestinal inflammation and their therapeutic potential for inflammatory bowel disease.
Harnessing Mucosal Immunity for Protective Vaccines -
A thorough review on mucosal immunity, the type of responses elicited, the unique anatomical and immunological features of the mucosal surfaces of the body, and the challenges associated with the generation of protective immunity via mucosal vaccines.
Sperm have long been thought of as streamlined DNA delivery vehicles, carrying little more than a fatherâs genes to the egg.
But a new study shows that in mice, sperm may transmit the fatherâs influence in another way.
During their passage through the epididymis, the coiled tube where they mature after leaving the testes, sperm pick up messenger RNAs (mRNAs), RNA transcripts of genes that contain the genetic instructions for making proteins.
These mRNAs seem to be transferred to the fertilized egg, where they may affect the developing embryo.
Your nose may be the gateway to a stronger immune system. đ
At the moment, an influenza vaccine called FluMist is the only licensed intranasal vaccine approved for use in humans. The vaccine is administered through a spray of fluid in the nose, rather than with an injection.
FluMist has proven effective in children, and is licensed for adultsâbut for a long time there has been no measurable âcorrelate of protection.â Scientists saw no sign of influenza-fighting immune cells circulating in the blood after adults received FluMist.
Now scientists at La Jolla Institute for Immunology (LJI) have discovered that FluMist can trigger an immune response directly in nasal tissue in adults. The vaccine trains immune cells in the upper nasal passages to recognize and fight influenza virus infection. This immune response stays in the upper airways and canât be detected via blood samples.
How do intranasal vaccines work? Can flu vaccines be better? Thrilled to announce our newest paper is out, demonstrating memory B cell responses in human upper airway after immunization with the intranasal flu vaccine (Flumist). Great findings by dedicated scientist Dr. Hannah Stacey in the lab, leveraging clever sampling techniques from Dr. Sydney Ramirez. La Jolla Institute for Immunology Science Magazine https://lnkd.in/gtRiyMdS
Since the start of this year, EUFOREA has partnered with 30+ international medical societies and patient organizations across pulmonology, allergology, and rhinology đ€. By breaking the silos between specialties, weâre working together to improve outcomes for patients affected by multimorbidities in the upper and lower airways.
Together with our academic and non-profit partners across Europe, the US, and the Middle East, weâre committed to tackling key unmet needs and raising the bar for global respiratory care. đ
The lung microbiome is increasingly recognized as a key contributor to the development and progression of chronic airway diseases. While these conditions are typically associated with reduced microbial diversity and pathogen overgrowth, emerging evidence suggests that non-pathogenic bacteria may...
#Immunology | đ§ đđČđčđčđ đŁđŒđđ¶đđ¶đŒđ» đ§đ”đČđșđđČđčđđČđ đ¶đ» đđŒđ-đąđ đđŽđČđ» đđŒđ»đČđ đđŒ đđŒđșđșđźđ»đ± đđđ»đŽ đđČđłđČđ»đđČ | University of Basel researchers led by Jean de Lima found that specialized helper T cells migrate to oxygen-scarce edges of immune hubs during lung infection. There, they produce the so-called HIF-1α protein and release interleukin-21, directing macrophages, B cells, and natural killer cells into coordinated responses against respiratory pathogens. Using advanced imaging in influenza-infected mice and inducible knockout models, the team mapped how these cells position at hub boundaries to orchestrate defense networks.
The findings show tissue-resident immune hubs function as command centers for on-site protection rather than antibody factories. Professor Carolyn King's group validated the mechanism across secondary influenza infections and lung cancer models, showing broad therapeutic potential. This breakthrough enables design of inhalable vaccines that build immune defense directly in airways where viruses enter, potentially transforming respiratory disease prevention. The spatial coordination strategy also opens perspectives for tissue-targeted therapies that use the body's natural positioning systems to strengthen local immune responses at infection sites.
đ Learn more & read the original publication: link in the comments đ
đšđ Follow #ScienceSwitzerland for the latest news and emerging trends on Swiss science, technology, education, and innovation >> swissinnovation.org Follow us >> Science-Switzerland #Science | #Education | #Research | #Innovation
Pre-eclampsia is often described as a disease of the placenta, but at its core it is also a disease of immune balance. When the maternal immune system becomes overactivated, the delicate vascular architecture of the placenta can begin to fail.
Recent data showing rising pre-eclampsia rates after the pandemic has prompted renewed interest in immune-vascular triggers. If spike protein interacts with macrophages and endothelial cells in the placenta, understanding that mechanism could become a crucial piece of the puzzle in protecting maternal and fetal health.
======================================================== Your Gut Readiness Assessment https://lnkd.in/ezPm4wht ========================================================
The global vaccine landscape may be entering a new phase â and oral vaccines are quickly becoming one of the most discussed innovations in infectious disease prevention. In recent industry conversations across biotech and pharmaceutical research communities in the U.S., more attention is shifting toward oral vaccine platforms. Unlike traditional injections, oral vaccines could simplify distribution, improve patient compliance, and make large-scale immunization campaigns far more accessible â especially in regions where healthcare infrastructure is limited. Several biotechnology companies are now accelerating research around oral delivery systems, mucosal immunity, and next-generation vaccine platforms. The idea is not only to prevent disease more effectively, but also to rethink how vaccines are manufactured, distributed, and administered globally. For pharmaceutical companies and healthcare systems, this shift could represent more than just a scientific breakthrough. It may reshape public health logistics, vaccine accessibility, and global pandemic preparedness in the coming decade. The question many people in the industry are asking now is: If oral vaccines become widely scalable, could they fundamentally change the way the world approaches infectious disease prevention? Curious to hear perspectives from people working across biotech, healthcare, and public health.
A very insightful review from the Akiko Iwasaki's group on the potential to harness mucosal immunity in next-generation vaccine development. While the rapid deployment of intramuscular mRNA vaccines was a landmark achievement in preventing severe COVID-19, intramuscular shots often fall short of providing sterilizing immunity. Mucosal immunity represents a particularly promising avenue for improving vaccines against respiratory viruses, as it enables immune protection to be established directly at the site of viral entry and early replication. Mucosal tissues, such as the respiratory tract, host locally regulated specialized immune cells that are functionally and spatially distinct. Reduction of infection and transmission requires engaging the mucosal immune response: a coordinated process beginning with epithelial pathogen sensing and culminating in the establishment of tissue-resident memory T (TRM) and B (BRM) cells, alongside robust local secretory IgA (SIgA) production. Unlike systemic IgG, nasal SIgA has demonstrated superior virus-neutralizing activity and greater breadth against antigenically drifted variants. A promising strategy for advancing vaccine design is the heterologous prime-boost approach. Research suggests that intramuscular priming (to establish peripheral memory pools) followed by an intranasal boost can effectively "pull" memory cells to the respiratory mucosa. However, the so-called 'mucosal' vaccines requires navigating complex physiological constraints, such as the mucociliary clearance system and the anionic mucus layer. Moreover, the regulatory path for mucosal vaccines is primarily hindered by the lack of validated correlates of protection, making it difficult to predict efficacy and guide clinical trial designs. Additionally, the anatomical proximity of the nasal mucosa to the central nervous system necessitates rigorous safety evaluations to prevent neuro-olfactory spillover or unintended neuro-inflammation. https://lnkd.in/eb5ZUMY4
Nasal spray vaccine could âreplace multiple jabs every yearâBookmark popoverRemoved from bookmarksClose popoverScientists at Stanford Medicine have developed a universal vaccine formula, tested on mice, that offers broad protection against various respiratory threats. The vaccine, delivered as a nasal spray, could protect against cold, flu, Covid, allergies, respiratory viruses, sepsis-causing bacteria, and even house dust mites. It works by mimicking the signals immune cells use to communicate during an infection, rather than targeting specific parts of a pathogen. If developed for humans, this vaccine could replace multiple annual jabs for winter respiratory infections and potentially protect against new pandemic bugs. While lead author Dr Bali Pulendran estimates human availability within five to seven years, other experts caution that a truly universal vaccine is still some way off due to safety considerations and the diversity of the human population.
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