๐ก๐ง๐ฎ๐ธ๐ฒ ๐ต๐ผ๐บ๐ฒ ๐บ๐ฒ๐๐๐ฎ๐ด๐ฒ ย โข IL-2/21 and IL-10/2 Trikines fuse a cytokine with a receptor-binding module to recruit a third receptor chain in cis, forming tri-receptor complexes that reprogram intracellular STAT signaling within the same cell. ย โข IL-2/21 Trikine enforces IL-2Rฮฒ/ฮณc and IL-21Rฮฑ co-engagement, generating pSTAT5 with IL-21-like pSTAT3, preserving stem-like CD8 T cells, limiting exhaustion, enhancing tumor control, and avoiding IL-2โdriven NK toxicity. ย โข IL-10/2 Trikine adds IL-2RฮฒโSTAT5 signaling to IL-10โdriven STAT3, boosting tumor infiltration and, with PD-1 blockade, expanding cycling TILs to suppress refractory lung and pancreatic tumors.
๐ฅ๐๐บ๐ฝ๐ฎ๐ฐ๐ ย โข AND-gated Trikines could replace cytokine cocktails and cell engineering, delivering tunable STAT programs with reduced systemic toxicity to overcome immunosuppression in solid tumors.
โ๐ข๐ฝ๐ฒ๐ป ๐พ๐๐ฒ๐๐๐ถ๐ผ๐ป๐ ย โข Which receptor-density thresholds best predict Trikine responsiveness across exhausted, stem-like, and regulatory T-cell states? ย โข Can modular Trikine architectures successfully decouple and exploit other pleiotropic profiles like STAT1/STAT4 pathways? ย โข Will human-reactive Trikines mirror murine pharmacokinetics and sustain patient TIL stemness during clinical translation
๐ฅ๐ฒ๐๐ถ๐ฟ๐ถ๐ป๐ด ๐ฆ๐ง๐๐ง ๐๐ถ๐ด๐ป๐ฎ๐น๐ถ๐ป๐ด ๐ณ๐ฟ๐ผ๐บ ๐๐ต๐ฒ ๐ฐ๐ฒ๐น๐น ๐๐๐ฟ๐ณ๐ฎ๐ฐ๐ฒ ๐๐ถ๐๐ต ๐ง๐ฟ๐ถ๐ธ๐ถ๐ป๐ฒ ๐ถ๐บ๐บ๐๐ป๐ผ๐๐ต๐ฒ๐ฟ๐ฎ๐ฝ๐ฒ๐๐๐ถ๐ฐ๐ Grayson E. Rodriguez, Yang Zhao et al Science, February 2026 Corresponding author: K. Christopher Garcia
DIU Immunologie et Biotherapies is a french diploma associating french universities and immunology laboratories. It is dedicated to the involvement of immunology in new biotherapies, either molecular or cellular.
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Shane Crotty (La Jolla Institute for Immunology) gives a comprehensive scientific review of immunological memory to vaccines with an emphasis on human vaccines and in humans.
This review covers the key adaptive immune components involved in vaccine-mediated protective immunity: B cells, CD8+ T cells, CD4+ T cells, and antibodies.
The video lecture will cover the same material as the written review (https://www.cell.com/immunity/fulltext/S1074-7613(26)00089-0) but is not a verbatim recitation of the review article. In the interest of flow, the video lecture will have very few citations. All citations are included in the written review; please refer to the review for references.
Video Chapters 00:00 Introduction to Immunological Memory 02:10 Introduction: Vaccine Impact on Health 05:55 Introduction: Circulating and Tissue Resident Memory Cells 06:06 Layers of Immune Protection 09:00 B-cell memory to vaccines: Introduction 09:50 B-cell memory to vaccines: Durability 35:12 B-cell memory to vaccines: Functionalities 56:00 B-cell memory to vaccines: Hybrid immunity and tissue resident memory 1:06:33 CD8 T-cell memory to vaccines: Durability 1:12:45 CD8 T-cell memory to vaccines: Functionalities 1:15:49 CD8 T-cell memory to vaccines: Durability part 2 1:17:27 CD8 T-cell memory to vaccines: Hybrid immunity and tissue resident memory 1:22:53 CD8 T-cell memory to vaccines: Summary 1:26:02 CD4 T-cell memory to vaccines: Durability 1:29:53 CD4 T-cell memory to vaccines: Functionalities 1:38:45 CD4 T-cell memory to vaccines: Hybrid immunity and tissue resident memory 1:43:15 CD4 T-cell memory to vaccines: Summary 1:44:58 Antibody memory to vaccines: Introduction 1:46:16 Antibody memory to vaccines: Durability 2:09:27 Antibody memory to vaccines: Functionalities 2:09:47 Antibody memory to vaccines: Hybrid immunity and tissue memory 2:15:04 Antibody memory to vaccines: Summary 2:16:05 Holistic understanding of immune memory to vaccines
Dans uneย revueย publiรฉe dansย Signal Transduction and Targeted Therapy, les scientifiques du laboratoireย ยซย Biologie du Cancer et Mรฉtabolismeย ยป (UMR 9018 CNRS/UPSaclay/Gustave Roussy, Villejuif) proposent une analyse approfondie consacrรฉe ร la voie mTOR (mammalian Target of Rapamycin), un rรฉgulateur central de la croissance cellulaire, du mรฉtabolisme et de lโhomรฉostasie. Cette voie de signalisation intรจgre de nombreux signaux intracellulaires et extracellulaires, tels que la disponibilitรฉ en nutriments, les facteurs de croissance ou le stress cellulaire, afin de coordonner les processus anaboliques et cataboliques, incluant la synthรจse des protรฉines, des lipides et des nuclรฉotides, lโautophagie et la dรฉgradation protรฉasomale. Sa dรฉrรฉgulation est impliquรฉe dans de nombreuses pathologies humaines.
ย
ร lโoccasion du cinquantiรจme anniversaire de la dรฉcouverte de la rapamycine, les auteurs proposent une synthรจse couvrant cinq dรฉcennies de recherche sur mTOR. Cette revue retrace lโรฉvolution historique du domaine, depuis la caractรฉrisation initiale des effets biologiques de la rapamycine jusquโร lโidentification de sa cible molรฉculaire et des voies de signalisation associรฉes. Elle met en perspective les connaissances fondamentales et rรฉcentes sur le rรดle de mTOR dans la plupart des champs de la biologie cellulaire et du dรฉveloppement, tout en soulignant lโessor des stratรฉgies thรฉrapeutiques ciblant cette voie.
ย
Une attention particuliรจre est portรฉe au dialogue รฉtroit entre la signalisation mTOR et la rรฉgulation mitochondriale. Cette interaction dynamique entre deux hubs mรฉtaboliques gouverne lโadaptation cellulaire, la survie, lโรฉquilibre รฉnergรฉtique et les dรฉcisions de destin cellulaire. Elle joue un rรดle clรฉ dans de nombreux contextes physiopathologiques, allant du cancer et du vieillissement aux maladies neurodรฉgรฉnรฉratives et aux troubles immunitaires.
Turning mosquitoes into "flying vaccines"? Science is getting creative in the fight against infectious diseases.
A fascinating new line of research explores how mosquitoes could be used to deliver vaccines to wild bats-helping stop dangerous viruses like rabies and Nipah at their source before they spill over into humans.
Here's the idea:
Mosquitoes are engineered to carry a harmless vaccine virus
When they bite bats, they "inject" immunity
Alternative approach: mineral-rich drinking stations with edible vaccines
Why this matters:
Bats are natural reservoirs for many high-risk viruses, and traditional vaccination methods simply don't work at scale in wild populations. Instead of culling (which can backfire), scientists are looking at ecological, non-invasive solutions.
Early results are promising:
Vaccinated animals developed protective antibodies
Bats were successfully immunized via bites, ingestion, and drinking
Some survived otherwise lethal virus exposure
Of course, big questions remain-especially around environmental safety, regulation, and real-world deployment.
But this approach signals something bigger: A shift toward stopping pandemics at the source, not just reacting to them. Innovations like this could redefine how we manage zoonotic diseases in an increasingly interconnected world.
Le Dr Isabelle Nel, PHU en Immunologie biologique ร l'Hรดpital Robert Debrรฉ, a rรฉcemment partagรฉ un article sur l'utilisation des anticorps thรฉrapeutiques.
The global vaccines market (excluding COVID-19 vaccines), valued at USD 49.59 billion in 2024, stood at USD 47.65 billion in 2025 and is projected to advance at a resilient CAGR of 7.3% from 2025 to 2030, culminating in a forecasted valuation of USD 67.91 billion by the end of the period.
The market is growing due to several factors, including the rapid development and global commercialization of vaccines, the increasing prevalence of infectious diseases that require vaccination for prevention, the rising number of immunization programs, advancements in technology that support vaccine development, and increased government support through investments and funding aimed at creating new vaccines for various disease indications.
โข The North America vaccines market accounted for a 52.3% revenue share in 2024.
โข By disease indication, the pneumococcal disease segment is expected to register the highest CAGR of 10.6%.
โข By technology, the inactivated & subunit vaccines segment is projected to grow at the fastest rate from 2025 to 2030.
โข By end user, the adult vaccines segment accounted for a larger share of 54.0% of the market in 2024.
โข Companies such as GSK, Merck Group, Pfizer were identified as some of the star players in the vaccines market (global), given their strong market share and product footprint.
โข Companies such as SINOVAC BIOTECH LTD., Incepta Pharmaceuticals Ltd., Valneva among others, have distinguished themselves among startups and SMEs by securing strong footholds in specialized niche areas, underscoring their potential as emerging market leaders
๐ Understanding Vaccination & Antibody Titre Dynamics in Dairy Cattle ๐งฌ
Effective vaccination is not just about injecting vaccinesโitโs about understanding how the immune system responds and how long protection lasts.
๐ฌ What happens after vaccination? The animalโs immune system produces antibodies. The first response is slow and low, while booster doses create a faster and stronger immunity.
๐ Antibody Titre Dynamics: Antibody levels follow a pattern: โก๏ธ Lag Phase โ ๐ Peak โ ๐ Decline
This is why timely booster doses are essential to maintain protection.
๐ฎ Maternal Antibodies in Calves:
- Obtained through colostrum - Provide early protection - Can interfere with early vaccination
โณ Proper timing of vaccination in calves is critical to avoid vaccine failure.
๐ Practical Vaccination Strategy:
- Calves: 3โ6 months - Boosters: 2โ4 weeks after first dose - Adults: Annual or biannual vaccination
The immune system can be your best friend for mRNA vaccines - and also your biggest bottleneck.
A new paper in npj Vaccines by Lobb et al., highlights a counterintuitive point: type I interferon (IFN), a key innate immune alarm signal, can reduce mRNA-LNP vaccine effectiveness if itโs triggered at the wrong time, because activated dendritic cells lose the ability to take up new antigen.
In their models, blocking IFNฮฑ/ฮฒ receptor signaling before vaccination (or removing the receptor specifically in dendritic cells) increased vaccine uptake/expression in DCs, improved CD8โบ T-cell priming, and led to better tumor control. They also show a practical implication: IFN already โin the systemโ (for example after an infection or a recent prior vaccination) can blunt the response to an mRNA-LNP vaccine given shortly afterwards.
This connects directly to a theme we care about at Sensible Biotechnologies: for mRNA medicines, purity and innate immune activation are not โnice-to-haveโ quality attributes - they can materially shape uptake, translation, and ultimately efficacy. If IFN signaling suppresses antigen acquisition and translation capacity in key antigen-presenting cells, then minimizing unnecessary innate triggers (including those driven by impurities) becomes part of the performance equation, not just the safety story.
Thatโs why Sensible is focused on maximizing mRNA purity and minimizing immunogenicity as we build a vertically integrated, cell-based platform for mRNA design and manufacturing.
From PK regulator to therapeutic breakthrough, FcRn is reshaping autoimmune treatment. With Vyvgart expanding into CIDP and Nipocalimab advancing in SLE and HDFN, the โchemical plasmapheresisโ era is accelerating.
As FcRn programs grow, precise control of pH-dependent binding is essential for long-acting mAb design and clinical success.
Il n'existe actuellement aucun traitement efficace contre l'insuffisance rรฉnale aiguรซ, qui est associรฉe ร des longues hospitalisations et un taux de (โฆ)
The interim futility analysis for cema-cel, just gave the lymphoma field something to think about. A 41.6% absolute difference in MRD negativity at Day 45 versus observation, with clean tolerability, availability in community hospitals and most patients managed as outpatients. It is a meaningful signal that allogeneic CAR-T can work in first-line consolidation post R-CHOP.
What about the patients who relapse after cema-cel? Go back to CD19 with an autologous product: Yescarta, Breyanzi? They all target the same CD19 as cema-cel. Would a second CD19 CAR-T be reimbursed? If cema-cel moves towards commercialization in LBCL, patients who relapse will need a subsequent differentiated option. The commercial case for CD19-targeted autologous therapies in this setting will need rethinking.
This is where eti-cel becomes relevant. A highly differentiated product also developed at Cellectis, on the same backbone as cema-cel (originated from Cellectis platform), eti-cel targets both CD20รCD22 simultaneously. Data at the current dose show 88% ORR and 63% CR in heavily pretreated patients, a strong signal for a dual allogeneic approach.
Fifteen years ago, CAR-T emerged as a revolution. The real breakthrough, the bona fide pharmaceutical product, is allogeneic. Off-the-shelf, scalable, standardized. It will establish a new order in cell therapy. Autologous therapies are a process and will, in time, disappear.
On in vivo CAR-T: the science is early, the toxicity profile remains unfavorable today, and the regulatory path for a therapy where the vector is the product is, at best, unclear.
Cellectis Allogene Therapeutics Kite Pharma Bristol Myers Squibb Novartis Johnson & Johnson Gilead Sciences #dlcl #CART #celltherapy #allogeneic | 14 comments on LinkedIn
VACCINES are most effective in harnessing the immune system to produce high levels of antibodies to stable and accessible targets. BUT, malaria parasites, HIV, and the influenza virus are capable of hiding their weakest parts from the immune system.
WHAT IF the immune system could be PROGRAMMED to produce high levels of those rare antibodies capable of finding and neutralizing the most vulnerable pathogenic features of these parasites? In this weeks issue of Science, Hartweger et al. (2026, Science 392, eadz8994) reported findings using a mouse model, in which they demonstrated that the self-amplification properties of the immune system could be harnessed to produce high levels of these rare neutralizing therapeutic antibodies. They used hematopoietic stem and precursor cells (HSPCs) to give rise to B lymphocytes activated to produce high titers of long-lasting neutralizing antibodies in mice that protected them from a lethal influenza infection.
Here is a news article highlighting this seminal research, and the avenues it has opened for future therapies for human diseases and infections:
A malaria vaccine showing up to 90% protection in early clinical studies and a key question: how does it work? Thatโs what the European CAPTIVATE consortium is working on. BPRC is a partner.
In Antwerp, researchers from across Europe came together to share progress and align next steps.
The CAPTIVATE consortium approach is fundamentally different. Instead of using fragments of the parasite, this vaccine uses a genetically attenuated version of the malaria parasite itself.
After vaccination, the parasite reaches the liver, but stops there. It cannot develop further. This allows the immune system to recognise and eliminate the parasite at the earliest stage, before it causes disease.
โThe strong protection seen in healthy volunteers often doesnโt translate to endemic settingsโ, says Erica Pasini (BPRC). โWe want to understand why and how to make it work where it matters most.โ
At BPRC, we contribute by studying immune responses in greater depth, helping to bridge the gap between controlled studies and real-world impact. Duringย the meeting, scientists shared the latest developments. Key project milestones have already been reached, and the work is in full swing!
Next step: in June, the first results of the non-human primate trial will become available along with key samples to further investigate the immune mechanisms behind protection.
Dans une revue publiรฉe dans Trends in Biochemical Sciences, Xia Xiao et Svetlana Dokudovskaya de lโUMR 9018 METSY (CNRS/UPSaclay/Gustave Roussy, Villejuif) font le point sur cinquante annรฉes de recherche autour de la rapamycine, une molรฉcule initialement dรฉcrite comme antifongique et devenue un pilier de la biologie moderne. Cet article, un Feature Review, a รฉtรฉ sรฉlectionnรฉ pour รชtre mis ร lโhonneur en couverture et sโinscrit dans la sรฉrie spรฉciale ยซย TIBS at 50: Foundations and Frontiersย ยป.
ย
Les auteurs retracent lโhistoire de la dรฉcouverte de la rapamycine ร partir dโรฉchantillons de sol de lโรฎle de Pรขques (Rapa Nui), et montrent comment lโรฉtude de cette molรฉcule a conduit ร lโidentification dโune voie de signalisation majeure, la voie TOR (Target of Rapamycin). Contrairement ร dโautres molรฉcules emblรฉmatiques comme la pรฉnicilline ou la ciclosporine, la rapamycine nโa pas seulement rรฉvolutionnรฉ des applications thรฉrapeutiques, mais a rรฉvรฉlรฉ un rรฉseau biologique entiรจrement nouveau.
ย
La revue met en lumiรจre le rรดle central de la voie TOR dans la rรฉgulation de la croissance cellulaire, du mรฉtabolisme, du vieillissement et de nombreuses pathologies. Elle souligne รฉgalement comment cette dรฉcouverte a permis dโintรฉgrer des domaines auparavant distincts, tels que le mรฉtabolisme et la signalisation cellulaire, en introduisant le concept de dรฉtection des nutriments comme mรฉcanisme clรฉ de rรฉgulation.
ย
Enfin, les auteurs discutent des perspectives actuelles et futures, illustrant lโimpact durable de cette dรฉcouverte, qui continue de structurer un champ de recherche en constante รฉvolution.
Things to Do and Not to Do When Vaccinating Birds ๐๐
โ Things to Do When Vaccinating Birds Use healthy birds only โ Vaccinate only birds that are active and disease-free.Only vaccinate healthy birds; postpone vaccination if the flock is showing signs of illness. Follow vaccination schedule โ Give vaccines at the correct age and time. Maintain cold chain (2โ8ยฐC) โ Keep vaccines in a refrigerator or ice pack.Bring them out of the cooler only when ready to use. Use clean water for vaccines โ Especially for drinking-water vaccines. Use sterile equipment โ Clean syringes and droppers should be used. Read manufacturerโs instructions โ Follow dosage and method carefully. Vaccinate early in the morning or evening โ Avoid heat stress. Withhold water for 1-4 hours before vaccination to ensure birds are thirsty. Mix vaccine properly โ Ensure even distribution in water or solution. Consider adding skim milk powder (about 2g per liter) to stabilize the vaccine. Ensure the vaccine is consumed within 1-2 hours. Record vaccination details โ Date, vaccine name, age of birds, batch number. Walk through the house to encourage birds to move around and drink or if in Battery cage system, ensure the nipples are not blocked. Observe birds after vaccination โ Monitor for reactions or stress.
โ Things Not to Do When Vaccinating Birds Do not vaccinate sick birds โ It may worsen their condition. Do not use expired vaccines โ They will not work effectively. Do not expose vaccines to sunlight or heat โ This destroys the vaccine. Do not mix vaccines with dirty water โ It reduces effectiveness. Do not use antibiotics before or after vaccination โ May affect vaccine response. Do not overcrowd birds during vaccination โ Causes stress. Do not open vaccine long before use โ Use immediately after opening. Do not use chlorinated water โ Chlorine kills live vaccines. Do not skip booster doses โ Immunity will be weak. Do not vaccinate during extreme weather โ Heat or cold affects immunity.
La ยซย reverse vaccinology 3.0ย ยป consiste ร utiliser lโintelligence artificielle (#IA) pour prรฉdire des structures antigรฉniques et dโinteractions anticorps-antigรจne. Elle a notamment menรฉ ร lโidentification dโune protรฉine utile ร la neutralisation de certaines formes de variole, variole bovine ou variole du singe.
Explications par Dr Emanuele Andreano, Ph.D., head of serology and immunology ร la Fondazione Biotecnopolo di Siena, ร lโoccasion des Journรฉes scientifiques 2026 de lโANRS Maladies infectieuses รฉmergentes.
โAdministered together with first-line TB drug therapy, our intranasal DNA fusion vaccine helped infected mice clear the disease bacteria faster, reduced lung inflammation and prevented relapse after treatment ended,โ says study lead author Styliani Karanika, M.D., a faculty member of the Johns Hopkins Center for Tuberculosis Research and assistant professor of medicine at the Johns Hopkins University School of Medicine.
โThe vaccine also helped the powerful TB drug combination of bedaquiline, pretomanid and linezolid work better, suggesting it could be used with treatments against drug-resistant TB to help the body fight the disease, even hard-to-treat cases.โ
Vaccines and Immunology: A Foundation of Preventive Medicine
One of the most impactful applications of immunology is vaccinationโa concept built on a simple yet powerful idea: training the immune system before exposure to disease.
The adaptive immune systemโs ability to developย long-term memoryย allows vaccines to provide lasting protection with minimal risk. This principle has transformed global health outcomes and continues to shape modern medical innovation.
Whatโs particularly remarkable is how advancements in biotechnologyโespecially mRNA platformsโhave accelerated vaccine development timelines without compromising safety or efficacy.
Vaccination is not only an individual health decision; it is aย collective responsibilityย that strengthens public health systems through herd immunity. As science continues to evolve, the role of immunology in preventive medicine will only become more critical.
The future of healthcare is not just about treating diseaseโbut preventing it.
The most critical strategy for controlling the spread of infectious diseases is vaccinationโmaking vaccine production processes pivotal to disease control and eventual eradication. Vaccination is an artificial process where inactivated, attenuated infectious pathogens, or their components, are delivered to the human body, using antigenic structures to activate the immune system. This process stimulates an effective response against specific pathogens to combat impending infections.
Since the mid-20th century, viral vaccines have been produced using chicken embryos, with dozens of approved traditional human vaccines manufactured via embryo-based processes. Today, however, cell culture-based vaccine production has become widespread: it enables simple infection and replication in controlled environments, with harvesting steps conducted in closed bioreactor systems to ensure sterility and further reduce biosafety risks through automation. This approach significantly boosts factory capacity, enabling the production of large quantities of vaccine doses.
The paper will be published in ๐๐ฐ๐ญ๐ฆ๐ค๐ถ๐ญ๐ข๐ณ ๐๐ฉ๐ฆ๐ณ๐ข๐ฑ๐บ this month.
Was this built in-house? Not really. It's the result of two strategic acquisitions that tell you exactly how big pharma is entering in vivo cell engineering.
Everything started about 8 years ago with Sanofi entering the mRNA therapeutics space first.
In 2018, Sanofi partnered with Translate Bio for mRNA vaccines. $45M upfront. Focusing specifically on up to five infectious diseases.
COVID hit.
They expanded the deal in 2020 to $300M cash + $125M as stock investment, covering all infectious diseases. Then in August 2021, they acquired the whole company for $3.2B!!!
What did they get? One of the largest private LNP libraries in the industry. mRNA manufacturing expertise. A platform ready to go beyond vaccines.
Tidal brought the missing piece: targeted nanoparticle technology to reprogram immune cells directly in the body.
Now the paper shows what happens when you combine both platforms.
The technical execution is solid:
โข Proprietary ionizable lipid 15 for T cell transfection โข Anti-CD8 VHH nanobody outperforming other ligands โข CD22 CAR benchmarked against clinically validated CARs (FMC63 and m971) โข Hepatic de-targeting, under 5% liver uptake โข Tumor suppression in aggressive human models
That last point matters. Getting mRNA into T cells is hard enough.
Keeping it away from liver trapping while maintaining efficacy is the real challenge.
They solved both.
This is how platforms get built in 2025. You don't develop everything internally. You acquire the best technology, integrate it fast, and publish validation data within a few years.
Translate Bio gave them the mRNA engine. Tidal gave them the targeting system. Together, they created an in vivo CAR-T platform neither could build alone.
The question now is whether improvements we witness in the in vivo CAR-T space will scale beyond hematological malignancies.
The delivery is transient. The safety profile looks clean (mRNA). Serial killing durability up to 8 days. And repeat dosing gave no signs of toxicity.
Can this match the persistence of ex vivo products? Will in vivo CAR-T platforms ever be efficacious in solid tumors?
So much money has been invested in this tech and we are seeing progress with creative solutions to optimize in vivo CAR-T platforms.
This weekโsย Global Health Notesย looks at how science and policy are shaping disease prevention โ from vaccineโcarrying mosquitoes and Indiaโs HPV rollout to new ways countries plan and fund vaccines.
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