The BATTLE RCT showed that #BCG vaccination may be preventive against #LongCovid (onlinelibrary.wiley.com/doi/… ). Now the researchers examined the effects on immune responses: dovepress.com/bcg-vaccinatio… Imho, we should take #trainedimmunity (more?) serious.

@virusesimmunity Dose is another open issue: the striking effect of intravesicular administration of #BCG (assoc. with \ risk of dementia in bladder cancer patients) may point to a higher #trainedimmunity effect from higher doses? (just a speculation) frontiersin.org/journals/imm…

1/2 An interesting link that #MECFS research may stand to benefit from? arstechnica.com/health/2026/… Interesting point: there may be a dose-response effect for establishing #trainedimmunity Wonder to which #BCG regimen this could translate? @VirusesImmunity

Want to learn how innate immune cells “remember” past threats and respond stronger next time? Check out our new book chapter on how histone modifiers link metabolism to gene activity in trained immunity. @tritocool @TrainedImmunity @IntechOpen intechopen.com/online-first/…

Introducing an IFN-γ–mediated strategy for enhancing immunity doi.org/10.1172/jci.insight.… Dearbhla M. Murphy @derv_murphy Sharee A. Basdeo @BasdeoLab & team report immune cells that defend against early infection can be trained to better fight tuberculosis and MRSA, especially in vulnerable individuals. The figure: IFN-γ induces trained immunity in human monocytes. Enriched monocytes were left untrained (UT; white) or trained with IFN-γ (10 ng/mL; gray) for 24 hours. Cells were differentiated into monocyte-derived macrophages. #TrainedImmunity

Trained immunity in cardiovascular disease: read more in EHJ. doi.org/10.1093/eurheartj/eh… #TrainedImmunity #CardiovascularDisease #Immunology #EHJ #Immunity #Cardiology @ESCardio @ESC_Journals

🔑A new key for “hard-to-treat” cancers? Train the immune system. A multi-institution team (Radboudumc Mount Sinai and others) reported in Science Advances that a bone marrow–targeting nanoparticle (MTP-HDL) can “train” innate immunity, easing the tumor’s immunosuppressive microenvironment and boosting checkpoint blockade (anti-PD-1/anti-CTLA-4) in mice. 🧬🛡️ It’s preclinical, but it points to a promising combo strategy for checkpoint-refractory solid tumors. Thank you to Dr. Willem J.M. Mulder [@WillemNANO], Bram Priem [@AngiogenesisA], @radboudumc #TrainedImmunity #NKcells #ScienceAdvances Disclaimer: This post explains medical and scientific information in an easy-to-understand way. Decisions about an individual’s diagnosis and treatment should be made in consultation with your treating clinician in the clinic. science.org/doi/10.1126/scia…

TRIM — Memory beyond T & B cells! Innate cells remember too. 🧠🔥 • First hit (BCG, β-glucan, infection) → epigenetic & metabolic rewiring • Next hit → stronger, faster, non-specific immune burst • Acts via monocytes, macrophages, NKs, progenitors • Boosts defense ✅ • But overdrive = inflammation/autoimmunity ⚠️ • Big potential for vaccine design & immunotherapy 🧬 🧩 Mechanism = histone marks glycolytic shift → “trained” state 📖 Latest Review: Trained Immunity: Reprogramming innate memory 👉 DOI: 10.1007/s11886-024-02167-7 (2024) #TrainedImmunity #InnateMemory #Immunology #Epigenetics #Vaccinology

Super pleased to share that I have been awarded a *UKRI Future Leaders Fellowship* @AberUni -to explore & characterise #trainedimmunity in cattle! Thank you for all the support along the way from colleagues, friends & my family! #Immunology #BCG #TB aber.ac.uk/en/news/archive/2…

🧬 The Trial That Quietly Validated the $NWBO Immune Engine Before there was Flaskworks. Before Bosch showed us the booster matrix. Before anyone whispered about Winterfell. There was a trial. And in that trial, they built the immune engine we are watching come online today. It happened without press releases. Without investor decks. Just data. Data that now aligns perfectly with the logic inside DCVax. And the immune system it activated? That system never turned off. 📍 Mayo Clinic. 2014. Silence in Plain Sight. At the Society for Immunotherapy of Cancer’s 29th Annual Meeting, a team from Mayo Clinic presented preliminary results from a pilot trial titled “Dendritic Cell Vaccine Treatment for Indolent B Cell Non-Hodgkin Lymphoma.” They tested two strategies. Both used autologous dendritic cells. Both pulsed those cells with tumor antigens. And both delivered immune responses that outlasted standard therapy. Arm A was cryoablation plus intratumoral injection. The tumor was frozen. Then dendritic cells were injected into the cryoablated lesion. This was in situ maturation. Arm B used excised tumor tissue. Lysate was prepared ex vivo. Dendritic cells were matured and pulsed with lysate. Then injected intradermally. This was systemic deployment. And both arms were boosted with Merck’s Pneumovax 23. This was not theoretical. This was immunologic engineering. 📈 The Results That Were Never Loud One patient reached a complete response. Five more reached partial responses. All told, half the patients in the trial responded. And the responses lasted. Some were still treatment free at 25 months. Others had not reached the threshold for next therapy at the time the data was presented. They used waterfall plots. You can see the signature. In Arm A, tumors melted. In Arm B, one tumor vanished completely. In both arms, the trend was unmistakable. No progression. No toxicity. No maintenance therapy. The immune system was carrying the load. And time to next treatment wasn’t measured in weeks. It was measured in years. 🧠 The Immune Terrain Was Rewritten Immune analysis showed a shift. Responders produced more interferon gamma. More IL-17a. Less IL-4. A clear Th1 Th17 profile. T helper 2 was shut down. They ran more than 40 immune phenotypes through flow cytometry. Clustered them. Mapped them. The responders had a distinct pattern. Their immune systems were reorganizing. Permanently. This was not a transient response. This was immune remodeling. And it happened after only 4 to 8 doses. 🧬 Why This Trial Was So Different Most immunotherapy trials test a molecule. This one tested a system. It used autologous monocyte-derived dendritic cells. Not from a factory. From each patient. It tested both in situ and ex vivo antigen delivery. It used real tumor signals. And then it combined those with Merck’s Pneumovax. Not to prevent infection. But to ignite immunity. It didn’t stop at tumor shrinkage. It tracked the entire immune conversion. Cytokine shifts. Cellular reprogramming. Systemic change. It proved that with the right antigen, the right cell, and the right booster, the body could take over. And it did all of this without checkpoint inhibitors. Without chemotherapy. Without needing to be repeated every three weeks. That is what makes this trial different. It wasn’t a test of tolerance. It was a test of theory. And the theory passed. 🔬 The Booster Was Already There Here’s what no one said out loud. In that trial, the dendritic cells didn’t work alone. They were paired with something routine. Something so ordinary that it became invisible. Pneumovax 23. Merck’s own vaccine. A pneumococcal polysaccharide used for decades to prevent infection in vulnerable adults. But in this trial, it was used for something else entirely. Not to stop disease. But to start immunity. It was injected intramuscularly before and during vaccine delivery. Not to fight pathogens. But to prime the innate immune system. To act as a nonspecific activator. A signal amplifier. A functional adjuvant for the DC vaccine. And it worked. Patients mounted durable anti-tumor responses. One entered complete remission. Others stayed off therapy for over two years. The booster, quiet, off-patent, overlooked, helped turn a cold immune system warm. And then it was forgotten. No follow-up. No branding. No campaign. Pneumovax returned to its lane. The trial faded. The immune principle it proved was buried beneath the noise. But that logic is still alive. And today, it has a new name. CAPVAXIVE. A next-generation pneumococcal conjugate vaccine, born from the same legacy but optimized for precision. And now, one of twenty growth drivers Merck is bringing to market. They will say it prevents pneumonia. But it may also do something else. Because the immune signal Pneumovax proved, the ability to wake up dendritic cells, to recruit antigen-presenting power, to turn a silent tumor into something the immune system can see, was already demonstrated. By Merck. By Mayo. By the immune system itself. And now, with CAPVAXIVE entering center stage, that signal may finally be ready to run the full circuit. From booster To dendritic payload To immune ignition To deployment This wasn’t a metaphor This was the first node in the network And the booster was already real 🧪 The Immune Stack Was Repeated And Got Even Stronger The Mayo trial using Pneumovax 23 wasn’t an isolated event. Over the following years, Mayo quietly ran three more trials that used the same core logic. Autologous dendritic cells. Intratumoral injection. And an immune booster. But this time, the booster was Prevnar13. Pfizer’s pneumococcal conjugate vaccine. And the architecture was unmistakable. Trial NCT03942328 in liver cancer used: High-dose radiotherapy to initiate tumor death Autologous dendritic cells, injected directly into the tumor Prevnar13 as the immune ignition layer No chemotherapy. No checkpoint inhibitor. Just immune programming, booster engagement, and response monitoring. The results were stunning. Sixty percent response rate in the first five patients. A two-year remission in cholangiocarcinoma. T cell receptor profiling confirmed memory cell emergence and new clonal expansion. Two additional trials layered in checkpoint inhibitors: NCT03035331 in non-Hodgkin lymphoma used pembrolizumab, cryoablation, and Prevnar13 with DCs NCT03325101 in metastatic melanoma followed the same logic Each trial followed the immune operating system. And each booster was chosen for its ability to reawaken trained immunity and amplify antigen visibility. Just like Pneumovax had done years earlier. Prevnar13 was developed by Wyeth, now owned by Pfizer. But the booster class is no longer a secret. Merck is building its own version. CAPVAXIVE. Because the logic doesn’t belong to a brand. It belongs to the immune system. 🏗️ What This Has to Do with Winterfell Everything. Winterfell is not a molecule. It is not a brand. It is not a metaphor. Winterfell is the physical deployment system Merck has now built to execute this exact architecture at global scale. Inside Building 50, Merck has constructed a modular cleanroom facility that is Flaskworks Eden compatible. That facility, backed by Emerson DeltaV automation and G-CON PODs, can run the entire workflow of this trial. From patient leukapheresis to dendritic cell maturation. From tumor lysate preparation to vaccine loading. From cryogenic control to QP release. Winterfell exists so this trial can be replicated 10000 times over. Flaskworks Eden is what turns Mayo’s manual process into an automated platform. CAPVAXIVE is what turns Pneumovax into a modern T dependent immune booster. WINREVAIR is what removes the suppressive signaling that held back the full potential of dendritic cells in the tumor microenvironment. And DCVax is what runs the immune engine they all plug into. Winterfell is the factory. Eden is the interface. Bosch is the booster array. NWBO is the logic owner. The 2014 trial was the rehearsal. This is the show. 📍 Who Was There This was not a speculative trial by unknowns. This was Mayo Clinic. This was Dr. Yi Lin. Dr. Michael Gustafson. Dr. Allan Dietz. Dr. Thomas Witzig. Dr. Stephen Ansell. The same people now cited in connection with dendritic cell manufacturing, GMP lysate, immune monitoring, and clinical translation of vaccine therapy. And that lysate method? The precise approach used in Arm B of the trial, where autologous dendritic cells were pulsed with ex vivo tumor lysate? That method is not generic. It is the patented, licensed, and protected intellectual property of Northwest Biotherapeutics. Covered by the Roswell Park license. And fully automated today by Flaskworks Eden. The trial did not just validate a general concept. It validated DCVax. It validated NWBO’s IP. And it showed, in human patients, that the method they now own produced long-lasting, booster-enhanced, T cell–driven immune control. The same infrastructure that now sits adjacent to Flaskworks. The same science that mirrors the structure of DCVax L and DCVax Direct. This wasn’t a coincidence. This was groundwork. 🔁 The Immune Engine Was Already Running They said dendritic cell vaccines couldn’t scale. They said cryoablation was fringe. They said Merck’s pneumonia vaccine couldn’t be part of cancer therapy. They were wrong. Because Mayo proved otherwise. In 2014. With the same architecture that NWBO now commands. With the same booster logic Merck now controls. With the same immune signature that the Bosch matrix now amplifies. So when you see CAPVAXIVE being called a blockbuster. When you hear WINREVAIR described as a platform modulator. When you see Flaskworks scaling in the background. And Winterfell going operational without headlines. Remember this. The immune system already responded. The blueprint already worked. The engine was already real. And the silence was not absence. The silence was alignment. ⚠️ Disclaimer This content is derived entirely from public records, peer-reviewed journal articles, clinical trial registries, patent databases, and official conference abstracts. Interpretations made herein are strategic in nature and do not reflect material nonpublic information. Clinical outcomes referenced are early phase and should not be assumed to predict future regulatory approvals. This content is provided for educational and analytical purposes only. #DCVax #Immunotherapy #CancerVaccine #CellTherapy #DendriticCells #TumorImmunology #ColdTumor #TrainedImmunity #PersonalizedMedicine #Flaskworks #BoschMatrix #EdenSystem #ProjectWinterfell #SI87 #CNPV #AutologousTherapy #CancerImmunology #GMPmanufacturing #BioManufacturing #ClinicalTrials #PrecisionMedicine #CancerBreakthrough #OncologyInnovation $MRK $MDCX $INDP $BGNE $BMY $PFE $AZN $LLY $IOVA

I'd love to connect if you're interested in trained immunity, eosinophils, allergy, or infection-driven inflammation! @ScienceMagazine #ScienceImmunology #PhDResearch #TrainedImmunity #Eosinophils #Asthma #Allergy #SkinInfection #InnateImmuneMemory

#epw2025 @CNIC_CARDIO it was great to present, together with Gillian Dunphy @Gillianoqr, our latest unpublished results in epigenetic regulation of #trainedimmunity & how a type-I IFN-#mitochondrial axis regulates efferocytosis and ISG induction in #macrophages

New publication, together with @LunaMinute @arlosdel on how mucosal #vaccines based on trained immunity (TIbVs) work to prevent respiratory infections — including MV130, developed by @Inmunotek #AMR #TrainedImmunity

Fantastic seminar today ⁦@ucdavis⁩ ⁦@ucd_physiology⁩ from ⁦@mario_manresa⁩ showing that fibroblasts remember prior exposure to inflammation - a possible example of #TrainedImmunity

Are you a researcher in #Immunology? Take a look at our call for papers in #TrainedImmunity ⬇️ elifesciences.org/inside-eli…

War übrigens schon VOR der #Pandemie immunologisch bekannt… #trainedimmunity nature.com/articles/s41577-0…

Congrats to #TeamKhanna's @Payalyokota on being awarded a scholarship and selected for a short talk for the Innate Imm Memory: Mech & Consequences Keystone Mtg in Vancouver, BC. Payal will talk about her ongoing work on #lungresMacs / #TrainedImmunity! keystonesymposia.org/confere…

Deep in scientific mode vs relaxing after a wonderful conference @iSTIIIMDD in Dresden. Wonderful opportunity to present some of the data I've been working on in #TrainedImmunity. Massive congratulations to @LedwithAnna for a fantastic presentation and winning a travel award 🎖️

🚨 Cues of trained immunity in macrophages of Multiple Sclerosis patients... Curious to know more? 🔍 Dive into our latest paper showcasing the fantastic work by Jennifer Fransson! 🧾✨ #MultipleSclerosis #TrainedImmunity #OpenAcess @InstitutCerveau neurology.org/doi/10.1212/NX…

8/11 🧫 Les 💉 à ARNm pourraient entraîner des altérations épigénétiques des cellules immunitaires innées, augmentant leur réactivité aux stimuli. #Immunité #TrainedImmunity 👉 ncbi.nlm.nih.gov/pmc/article…