Innovative Techniques for Vaccine Development

How to Build a Pandemic-Ready Vaccine in a Ball You Can Store in Your Backpack without freezing it! Imagine if vaccines didn’t need fancy deep freezers. Imagine if they could survive the heat, travel far, and still do their job — all while being smarter, safer, and faster to produce. That’s not fiction anymore. It’s Nanoball mRNA technology from Japan’s Nagasaki University, in partnership with NEC’s AI team and global health leader CEPI. What is a Nanoball? It’s a tiny, engineered ball made from a substance called polyglutamic acid — a biodegradable material that protects the mRNA inside, like how a box protects a fragile item during shipping. Instead of using conventional lipid nanoparticles (the fat bubbles used in most mRNA vaccines), these nanoballs offer: More stability (can be freeze-dried and kept at room temperature) Better protection (resists enzymes that normally break down mRNA) Easier distribution (no ultra-cold freezers needed) Wait, how does it get inside the body’s cells? Good question. Normally, both the nanoball and your cell surface have a negative charge — and in science, two negatives repel. But thanks to nano-scale design, the ball enters cells using a natural process called endocytosis — it’s like the cell gently absorbs it instead of pushing it away. Once inside, it releases the mRNA, which tells your body how to make a harmless piece of the virus — and trains your immune system to fight the real thing if it ever shows up. So why is AI involved? Designing a vaccine isn’t just about wrapping mRNA. It’s about choosing exactly which part of the virus to teach the body to recognize. That’s where NEC OncoImmunity’s AI comes in. It scans thousands of virus proteins to pick the best pieces — ones that will trigger a strong immune response and work across different virus strains. It’s like finding the perfect target to train your immune army with maximum efficiency. Why should we care? Because this tech could: Speed up vaccine creation in a future pandemic Reduce costs and cold storage headaches in low-income regions Enable local manufacturing during outbreaks In short: It makes vaccines smarter, tougher, and fairer. Backed by CEPI and built for the 100 Days Mission CEPI, the global group funding pandemic innovation, has invested $5 million into this project — aiming for a world where vaccines can be made within 100 days of detecting a new threat. With freeze-dried nanoballs and AI-designed antigens, that goal just got a lot closer. Bottom line? The next generation of vaccines might come in shelf-stable, AI-optimized nanoballs not ice-cold vials. And that might just be the upgrade our immune systems and our supply chains desperately needed. Suchitaa Paatil Sanju S Amit Saxena Ajay Nandgaonkar Anju Goel Taruna Anand #VaccineInnovation #AIinHealthcare #PandemicPreparedness #NanoballTech #mRNA #GlobalHealth

Immune-boosting bacterial platform could aid nasal vaccines Outer membrane vesicles (OMVs) are non-living spherical #nanostructures that derive from the cell envelope of Gram-negative #bacteria. OMVs are important in bacterial #pathogenesis, cell-to-cell communication, horizontal #gene transfer, quorum sensing, and in maintaining bacterial fitness. These structures can be modified to express #antigens of interest using glycoengineering and genetic or chemical modification. The resulting #OMVs can be used to immunize individuals against the expressed homo- or heterologous antigens. Additionally, cargo can be loaded into OMVs and they could be used as a #drugdelivery system. OMVs are inherently #immunogenic due to proteins and glycans found on Gram negative bacterial outer #membranes. OMVs—non-infectious particles naturally released by some bacteria that are known to boost immunity—can enhance intranasal vaccines, strengthening levels of #protection at the point of #pathogen entry so those #vaccinated not only avoid getting sick but also avoid passing on the #infection to others. Abera Bioscience AB’s preclinical studies have shown their OMV-based platform triggers strong #immune responses against various bacterial and viral pathogens, inducing #mucosal immunity. Bacterial OMVs is being investigated for boosting mucosal immunity—which is believed could be key to stopping the onward transmission of several #viruses. Abera Bioscience researchers are modifying OMVs, developed on their proprietary vaccine platform, BERA, with antigens produced by cell-free-production methods, resulting in new immune-boosted nasal #vaccine sprays and powders. OMVs can be stockpiled and, in the event of a new pathogen threat, could be quickly coupled with different antigens to accelerate the #development of new vaccines. The plug-and-play #innovation also supports accessible pricing, facilitates #technology transfer, and has a favourable thermostability profile, all of which are beneficial qualities for LMICs. References: [1] https://lnkd.in/ghi38Bjt; [2] https://lnkd.in/gEtYjVB9 [3] https://lnkd.in/gHwaWbEV; [4] https://lnkd.in/gKsBXTg5 [5] https://lnkd.in/g-4xRS92; [6] https://lnkd.in/gKmJQUyY

Researchers describe a nasally delivered “universal vaccine” strategy that, in mice, provided broad protection against multiple respiratory threats for at least three months. The approach is positioned as a potential seasonal, pre-winter intervention that could offer a first line of defense not only against well-known viruses such as #SARSCoV2 (which causes #COVID19) and #influenza, but also against a range of respiratory pathogens more generally - and possibly help blunt impacts from future #pandemics IF it proves safe and effective in humans. ▪️ The work is led by Prof Pulendran Bali, an immunologist at Stanford University. Pulendran’s group builds on earlier insights from studying the Bacillus Calmette–Guérin (#BCG) #vaccine, which can provide temporary, broad, non-specific protection by stimulating the innate #immunesystem. Unlike conventional vaccines that primarily train the adaptive immune system (B cells and T cells) to recognize specific #pathogen proteins, this new strategy aims to “supercharge” innate defenses also enhancing the ability of respiratory epithelial cells (a frequent target of respiratory pathogens) to resist infection. ▪️The vaccine described uses three components. Two are drugs designed to stimulate receptor proteins that activate innate immune cells such as lung macrophages. The third component engages a subset of #Tcells in the adaptive immune system, whose role is to keep sending sustaining signals so the innate immune system remains in an activated, protective state. The formulation includes an immunogenic protein from chicken eggs; when that component was omitted in experiments, the protective immunity declined quickly. ▪️After four nasal doses, mice showed immunity not only to SARS-CoV-2 and other coronaviruses, but also to bacteria that cause certain respiratory infections. A notable additional effect was suppression of hypersensitivity pathways involved in allergy: the activated immune pathways reduced responses to house dust mites, helping to prevent allergic asthma in the mouse model. ▪️Mechanistic analyses suggest what Pulendran calls a “two-bulwark” system: an initial mucosal barrier reduces pathogen entry into the lungs, and a second layer rapidly mobilizes the pathogen-specific immune response to eliminate any invaders that get through. 🗃️ See comments section for reference.

A simple trick to improve vaccine efficacy. Vaccine design often revolves around the design of either antigen or adjuvant. However, in our latest paper led by Morgan Janes, PhD, we show that a simple addition of a polyphenol to the vaccine formulation increases its persistence at the injection site, and it subsequently increases its exposure to the immune microenvironment, a strategy we call a TAPER vaccine. The result is a significant improvement in the antibody titers against the antigen. TAPER vaccine durably improved humoral response against the receptor-binding domain (RBD) of SARS-CoV-2 while concomitantly enhancing the antigen-specific T cell response. https://lnkd.in/eTiPpWEy Owing to simplicity and ultra-low cost, TAPER vaccine offers a potential tool to improve vaccination outcomes at a larger scale. Alex Gottlieb Charles Park Shrinivas Acharya Griff Bibbey #vaccination #immunization #infectious_disease

Revolutionizing mRNA vaccine delivery with piezoelectric electroporation: when the need of LNPs is simply not there. In a new study (just published as a pre-print), researchers have introduced Piezopen, a novel device for enhancing "naked" RNA vaccine delivery. Here's what you should know about this innovative approach: 1) Cost-effective and simple - Piezopen is an inexpensive (less than $1), battery-free, handheld device utilizing piezoelectric electroporation with microneedle electrodes to deliver mRNA directly into cells without needing LNPs. 2) Comparable efficacy to LNPs - The study demonstrates that Piezopen can deliver naked mRNA, self-amplifying RNA (saRNA), and circular RNA (circRNA) with gene expression and immune responses akin to those achieved by state-of-the-art LNPs. This includes robust responses against SARS-CoV-2 mRNA with minimal reactogenicity, even at low doses. 3) Enhanced vaccine durability - Piezopen's method not only matches the immunogenicity of LNPs but does so with improved durability. Gene expression persisted significantly longer, suggesting potential for enhanced vaccine longevity and effectiveness. 4) Translatability across species - The technology has been validated in both rodents and ex vivo human skin, showing promising results for translating this approach into clinical settings. This cross-species efficacy is crucial for moving from preclinical to human trials. 5) Reducing systemic inflammation - Unlike LNPs, which can cause significant inflammation, Piezopen's localized delivery to the epidermis minimizes systemic reactogenicity, offering a safer alternative for RNA vaccine administration. This advancement challenges the current paradigm of RNA vaccine delivery, proposing a pathway for more accessible, effective, and less inflammatory mRNA vaccines. By potentially reducing the need for complex LNPs, Piezopen could democratize mRNA vaccine technology, enhancing global vaccination efforts. Learn more about the article here: https://lnkd.in/e4e3h9P4 #mRNAVaccines #VaccineTechnology #InnovationInHealthcare #RNATherapeutics #Electroporation

🧬 mRNA vaccines… that build 𝘵𝘩𝘦𝘪𝘳 𝘰𝘸𝘯 𝘯𝘢𝘯𝘰𝘱𝘢𝘳𝘵𝘪𝘤𝘭𝘦𝘴 inside your body? 𝗩𝗮𝗰𝗰𝗶𝗻𝗲𝘀 have saved 𝟭𝟱𝟰 𝗺𝗶𝗹𝗹𝗶𝗼𝗻 𝗹𝗶𝘃𝗲𝘀 in the last 50 years. The greatest healthcare invention ever! And after COVID, we all know the power of 𝗺𝗥𝗡𝗔 𝘃𝗮𝗰𝗰𝗶𝗻𝗲𝘀. But they’re not the only ones! Can we mix modalities and get better vaccines? Exactly what the authors of this paper thought! They combined mRNA vaccines and protein nanoparticle vaccines, hoping that each would bring their immunological advantages: - mRNA: Intracellular antigen expression, robust CD8 T cell activation, and rapid manufacturing. 🧬 - Protein nanoparticles: Strong B cell activation and neutralizing antibody responses. Instead of injecting a pre-made nanoparticle, the researchers designed an mRNA vaccine that encodes a 𝘀𝗲𝗹𝗳-𝗮𝘀𝘀𝗲𝗺𝗯𝗹𝗶𝗻𝗴 𝗽𝗿𝗼𝘁𝗲𝗶𝗻 𝗻𝗮𝗻𝗼𝗽𝗮𝗿𝘁𝗶𝗰𝗹𝗲. Cells take up the mRNA → produce protein subunits → and those assemble into a 𝟲𝟬-𝗺𝗲𝗿 𝗽𝗮𝗿𝘁𝗶𝗰𝗹𝗲, displaying viral antigens all over the surface. They dubbed this approach: mRNA-launched vaccines! Super cool. Here’s the build: — A computationally designed icosahedral scaffold   — Fused to a stabilized SARS-CoV-2 antigen (Rpk9, RBD variant)  — Delivered via lipid nanoparticles And the results? In mice, these mRNA-launched vaccines: — Produced 𝟰× 𝗵𝗶𝗴𝗵𝗲𝗿 𝗮𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝘁𝗶𝘁𝗲𝗿𝘀 than standard mRNA vaccines 🧫  — Reached similar protection at ~𝟮𝟱× 𝗹𝗼𝘄𝗲𝗿 𝗱𝗼𝘀𝗲𝘀  — Generated strong neutralizing antibodies across variants  — Fully protected against viral challenge (no detectable virus in lungs!) All while keeping the T-cell response. Incredible! A great example of 𝗿𝗮𝘁𝗶𝗼𝗻𝗮𝗹 𝘃𝗮𝗰𝗰𝗶𝗻𝗲 𝗱𝗲𝘀𝗶𝗴𝗻, which merges the strengths of two platforms! Of course, the authors know the limitations:  — in vivo assembly and stability  — translation to humans  — manufacturing and scalability But it’s so cool! Could it be a new age for vaccines? PS: Read the full write-up here! https://lnkd.in/esSxxNfu ------ Ciao, I'm Marco! 👋 I post about protein design, DNA nanotech, and synthetic biology. If you like my content, follow me to see more!

mRNA Vaccines for HIV Trigger Strong Immune Response in People – For the first time a clinical trial shows the generation of neutralizing antibodies against an HIV clinical trial using mRNA technology. The results of an early-stage trial show that about 80% of participants who received one of two mRNA HIV vaccine candidates produced potent antibodies against the viral envelope. By contrast, only 4% of the participants who received the unbound-protein vaccine produced corresponding antibodies. Unlike other vaccines that use soluble envelope (Env) proteins to design antigens, two studies describe the use and efficacy of an mRNA approach to produce membrane-bound versions of a stabilized native-like Env trimer (BG505 MD39.3). One study demonstrates with preclinical models (rabbits and non-human primates) that the elicited antibodies  bound to the intended, non-base regions of the Env. Another publication shows preliminary findings from a phase I trial in humans that shows that vaccination of humans with a membrane-bound Env trimer elicits productive antibody responses. In addition to delivering membrane-bound antigens,  which led to stronger nAb responses compared with mRNA-encoded soluble Env, mRNA technology also facilitates fast increased production and reduces the cost of vaccine manufacturing compared to traditional approaches. https://sco.lt/5i1cp6 #HIV #vaccines #nAb #mRNA #Moderna #Pfizer #health #globalhealth #publichealth #biotechnology #pharmaceuticals #medicine #CDC #WHO #ECDC #NIH #NIAID

🔬 𝐄𝐧𝐡𝐚𝐧𝐜𝐢𝐧𝐠 𝐦𝐑𝐍𝐀 𝐕𝐚𝐜𝐜𝐢𝐧𝐞 𝐂𝐡𝐚𝐫𝐚𝐜𝐭𝐞𝐫𝐢𝐳𝐚𝐭𝐢𝐨𝐧 𝐰𝐢𝐭𝐡 𝐌𝐒 🧬💡 The rapid evolution of 𝐦𝐑𝐍𝐀-𝐛𝐚𝐬𝐞𝐝 𝐯𝐚𝐜𝐜𝐢𝐧𝐞𝐬 has revolutionized infectious disease prevention, but ensuring their 𝐪𝐮𝐚𝐥𝐢𝐭𝐲, 𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧𝐚𝐥𝐢𝐭𝐲, 𝐚𝐧𝐝 𝐭𝐫𝐚𝐧𝐬𝐥𝐚𝐭𝐢𝐨𝐧 𝐟𝐢𝐝𝐞𝐥𝐢𝐭𝐲 remains a critical challenge. A new study from Merck introduces an 𝐚𝐧𝐭𝐢𝐛𝐨𝐝𝐲-𝐟𝐫𝐞𝐞, 𝐩𝐥𝐚𝐭𝐟𝐨𝐫𝐦-𝐛𝐚𝐬𝐞𝐝 𝐌𝐒 𝐰𝐨𝐫𝐤𝐟𝐥𝐨𝐰 to assess mRNA vaccine integrity, overcoming limitations in traditional immunodetection methods. 📌 𝐊𝐞𝐲 𝐚𝐝𝐯𝐚𝐧𝐜𝐞𝐦𝐞𝐧𝐭𝐬: 🧪 𝐂𝐞𝐥𝐥-𝐅𝐫𝐞𝐞 & 𝐂𝐞𝐥𝐥-𝐁𝐚𝐬𝐞𝐝 𝐓𝐫𝐚𝐧𝐬𝐥𝐚𝐭𝐢𝐨𝐧 𝐰𝐢𝐭𝐡 𝐌𝐒: Enables rapid, 𝐚𝐧𝐭𝐢𝐛𝐨𝐝𝐲-𝐢𝐧𝐝𝐞𝐩𝐞𝐧𝐝𝐞𝐧𝐭 𝐝𝐞𝐭𝐞𝐜𝐭𝐢𝐨𝐧 of translated proteins, ensuring precise sequence confirmation and relative quantification. 🛠️ +𝟏 𝐑𝐢𝐛𝐨𝐬𝐨𝐦𝐚𝐥 𝐅𝐫𝐚𝐦𝐞𝐬𝐡𝐢𝐟𝐭𝐢𝐧𝐠 𝐃𝐞𝐭𝐞𝐜𝐭𝐢𝐨𝐧: Identifies off-target protein translation induced by 𝐍𝟏-𝐦𝐞𝐭𝐡𝐲𝐥𝐩𝐬𝐞𝐮𝐝𝐨𝐮𝐫𝐢𝐝𝐲𝐥𝐚𝐭𝐢𝐨𝐧, providing insights for optimizing mRNA sequence design. ⚖️ 𝐌𝐮𝐥𝐭𝐢𝐯𝐚𝐥𝐞𝐧𝐭 𝐕𝐚𝐜𝐜𝐢𝐧𝐞 𝐀𝐬𝐬𝐞𝐬𝐬𝐦𝐞𝐧𝐭: Resolves analytical challenges in mRNA mixtures with 𝐡𝐢𝐠𝐡 𝐬𝐞𝐪𝐮𝐞𝐧𝐜𝐞 𝐡𝐨𝐦𝐨𝐥𝐨𝐠𝐲, allowing 𝐬𝐢𝐦𝐮𝐥𝐭𝐚𝐧𝐞𝐨𝐮𝐬 𝐩𝐫𝐨𝐭𝐞𝐢𝐧 𝐪𝐮𝐚𝐧𝐭𝐢𝐟𝐢𝐜𝐚𝐭𝐢𝐨𝐧 from multiple antigens. 🔥 𝐒𝐭𝐚𝐛𝐢𝐥𝐢𝐭𝐲-𝐈𝐧𝐝𝐢𝐜𝐚𝐭𝐢𝐧𝐠 𝐀𝐬𝐬𝐚𝐲𝐬: Monitors mRNA degradation under thermal stress to evaluate impact on antigen translation and vaccine potency. 💡 𝐖𝐡𝐲 𝐢𝐭 𝐦𝐚𝐭𝐭𝐞𝐫𝐬? This 𝐋𝐂-𝐌𝐒/𝐌𝐒-𝐛𝐚𝐬𝐞𝐝 𝐚𝐩𝐩𝐫𝐨𝐚𝐜𝐡 offers a 𝐬𝐜𝐚𝐥𝐚𝐛𝐥𝐞 𝐚𝐧𝐝 𝐩𝐫𝐞𝐜𝐢𝐬𝐞 analytical solution for assessing mRNA vaccine quality—critical for 𝐚𝐜𝐜𝐞𝐥𝐞𝐫𝐚𝐭𝐢𝐧𝐠 𝐯𝐚𝐜𝐜𝐢𝐧𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 against rapidly evolving pathogens. 🔎 Read the full study below! ⬇️ #mRNA #Vaccines #MassSpectrometry #AnalyticalScience #Biopharma Alyssa Stiving, Ben Roose, Christopher Tubbs, Mark Haverick, Ashley Gruber, Richard Rustandi, Jesse Kuiper, Matt Schombs, Hillary Schuessler, PhD & Xuanwen Shawn Li

Functionality and translation fidelity characterization of mRNA vaccines using platform-based mass spectrometry detection Recently published in Nature Portfolio Journal, Vaccines, researchers from Merck developed a new analytical method combining cell-free translation (CFT) and liquid chromatography - mass spectrometry to detect, characterize, and quantify antigen proteins from #mRNA constructs. This approach enabled: - Evaluation of mRNA functionality under thermal stress - Assessment of multivalent formulations with high sequence homology - Identification of +1 ribosomal frameshifting linked to N1 - methylpseudouridylation. The CFT-MS method [conducted on an #Evosep One (Evosep Biosystems) coupled to a Thermo Fisher Scientific Orbitrap Exploris 480 mass spectrometer] demonstrated high sensitivity and specificity, accurately identifying all six translated proteins from a hexavalent mRNA drug product in a dose-dependent manner. It was found that cleanup of the peptides in the #Evotip, was critical due to the viscous nature of the cell-free translation system. This platform-based approach eliminates the need for antibodies, making it a valuable analytical approach for assessing mRNA quality and functionality in vaccine development, potentially accelerating the response to rapidly mutating pathogens like SARS-CoV-2 and influenza or other emerging infectious diseases. The full manuscript can be read here: https://lnkd.in/eHeVYrCP Congratulations to the team for this impressive work: Alyssa Stiving, Ben Roose, Christopher Tubbs, Mark Haverick, Ashley Gruber, Richard Rustandi, Jesse Kuiper, Matt Schombs, Hillary Schuessler, PhD, Xuanwen Shawn Li

Needles may soon be a thing of the past. Scientists created a vaccine cream that triggers the same immune response as a shot — simply by rubbing it onto the skin. In a study published in Nature, researchers at Stanford University used Staphylococcus epidermidis, a naturally occurring skin bacterium, to stimulate immunity in laboratory mice. By bioengineering the bacteria and applying it topically, the mice developed antibodies and stayed protected—even when exposed to lethal doses of tetanus toxin. The science lies in a bacterial protein called Aap, which helps activate the immune system through sentinel cells in the skin. Humans, who already host S. epidermidis, could one day receive vaccines painlessly through creams instead of shots. “We all hate needles,” said Dr. Michael Fischbach, who led the research, adding that this method might also avoid the inflammation typically caused by injected vaccines. The next step? Testing on primates before moving to clinical trials. If successful, this innovation could revolutionize vaccinations, offering a painless, needle-free alternative for protecting against viruses, bacteria, and parasites. Learn more: https://lnkd.in/dGCs7NbK