Vaccine Development Insights

Nucleic acid vaccines have grown in importance over the past several years, with the development of new approaches remaining a focus. We describe a lipid nanoparticle-formulated DNA (DNA-LNP) formulation which induces robust innate and adaptive immunity with similar serological potency to mRNA-LNPs and adjuvanted protein. Using an influenza hemagglutinin (HA)-encoding construct, we show that priming with our HA DNA-LNP demonstrated stimulator of interferon genes (STING)-dependent upregulation and activation of migratory dendritic cell (DC) subpopulations. HA DNA-LNP induced superior antigen-specific CD8+ T cell responses relative to mRNA-LNPs or adjuvanted protein, with memory responses persisting beyond one year. In rabbits immunized with HA DNA-LNP, we observed immune responses comparable or superior to mRNA-LNPs at the same dose. In an additional model, a SARS-CoV-2 spike-encoding DNA-LNP elicited protective efficacy comparable to spike mRNA-LNPs. Our study identifies a platform-specific priming mechanism for DNA-LNPs divergent from mRNA-LNPs or adjuvanted protein, suggesting avenues for this approach in prophylactic and therapeutic vaccine development. Interesting study detailing the development of a nucleic acid vaccine platform using lipid nanoparticle-formulated DNA (DNA-LNP), by Nicholas Tursi and larger team at The Wistar Institute and University of Pennsylvania Perelman School of Medicine: https://lnkd.in/dCvxV4y5 Additional information on companies involved in Nucleic Acid Vaccine Development and Lipid Nanoparticle (LNP) Drug Delivery for those interested: INOVIO Pharmaceuticals, Inc. Arcturus Therapeutics Moderna BioNTech SE Tonix Pharmaceuticals Immunomic Therapeutics, Inc. PDC*line Pharma Oxford Biomedica Entos Pharmaceuticals Pfizer Enara Bio GeoVax Labs, Inc. Valo Therapeutics Ltd Acuitas Therapeutics Evonik FORMUMAX SCIENTIFIC INC. GenScript FUJIFILM Pharmaceuticals U.S.A., Inc. Prorenata Biotech Camurus Ethris

In 2010, a historic collaboration—led by African governments, World Health Organization, PATH, and the Serum Institute of India Pvt. Ltd.—resulted in MenAfriVac, the first vaccine developed specifically to meet the needs of the African meningitis belt. Priced at less than $0.50 per dose, it targeted meningitis A, which caused 80% of regional outbreaks. The impact was transformative: over 360 million people vaccinated in just 10 years, a 99% drop in meningitis A, and more than one million lives saved. This success reflects the leadership of African governments, the dedication of local health workers, and the power of transformative global partnerships. My colleague Greg Widmyer highlights how this story exemplifies what Gavi, the Vaccine Alliance has achieved over 25 years—helping halve global childhood deaths and supporting vaccine production in many low- and middle-income countries. Today, 19 former Gavi-supported countries are financing their own programs and even contributing as donors. Sustained global solidarity is essential to ensure every child, everywhere, can access vaccines that protect their health and future. 📖 Read more: https://lnkd.in/eYh2GvkE

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

I’ve been working in #mRNA for nearly a decade now—well before the COVID-19 pandemic brought it into the spotlight. What follows are my personal views, not those of my employer, but I wanted to share them because I think we’re at an inflection point—and not in a good way.   It’s one thing if people choose not to take a vaccine. That’s their right. But when that personal decision turns into legislation that prevents others from accessing mRNA-based medicines, that crosses a line. Right now, we’re seeing bills introduced in states like Texas, Kentucky, Idaho, and South Carolina that propose banning mRNA therapies—sometimes just for infectious diseases, and sometimes more broadly.   And here's the part that often gets missed: mRNA is not just about vaccines. It’s a platform with enormous potential in oncology, cardiometabolic disease, autoimmune disorders, and beyond. Some of the most exciting innovation in biotech today—like personalized cancer vaccines and regenerative medicine approaches—relies on the very mRNA tools now under threat.   At the federal level, NIH has already pulled at least one mRNA-related grant and is collecting information on others. Scientists are being advised, unofficially, to remove references to mRNA from new grant proposals altogether. That chilling effect is already pushing some of the brightest minds in our field to seek opportunities abroad. (See articles in Financial Times , The Guardian and Nature last month alone.)   I’ve spoken with a number of industry peers recently who are relocating to Asia, where interest and investment in mRNA remain strong. I understand their decision—but I’m also heartbroken. We’re forcing talent out. We’re stifling innovation. And we’re jeopardizing our standing as a global leader in biotech.   We are undermining our own future—and pretending it’s in the name of freedom. We are better than this. We can do better than this.

I am happy to share about our collaborative research on enhancing Intranasal Influenza vaccines has just been published in the American Chemical Society (ACS) Nano on 15th February 2025! This project was a fantastic collaboration between Georgia Institute of Technology , Georgia State University and Tokyo University of Science. A novel approach using layer-by-layer (LBL) nanoparticles to improve the delivery and effectiveness of intranasal flu vaccines has been developed. We have created nanoparticles coated with alternating layers of mucoadhesive and muco-inert materials, allowing for better nasal delivery and interaction with immune cells. This approach significantly boosts both cellular and humoral immune responses, leading to enhanced protection against influenza in mice. High IgA titers, was observed which is a hallmark of potent mucosal immunity and persistence of immune responses. This work demonstrates the importance of designing effective intranasal vaccines to provide robust protection against influenza. Read more: https://lnkd.in/e6dSU8xJ Follow ⚜️ Surya Sekhar Pal ⚜️ for more! #influenza #flu #immunity #vaccine #development #sciencecommunication #researchers #scientistlife #collaborations #respiratorydiseases #linkedinfamily #linkedinforcreators #follow

🟥 Exosome Vaccines for Immunotherapy Exosomes are ideal carriers for cancer and infectious disease vaccine development because they are derived from various cell types, are biocompatible, and can carry antigens, nucleic acids, and immunomodulatory molecules. Therefore, exosome-based vaccines are a breakthrough innovation in immunotherapy, characterized by the use of the natural properties of exosomes to enhance immune responses. Exosomes derived from tumor cells or modified to carry tumor-associated antigens can effectively deliver these antigens to dendritic cells (DCs). This process can stimulate the activation of cytotoxic T lymphocytes (CTLs), enhancing the body's ability to recognize and attack tumor cells. Some tumor-derived exosome vaccines have shown promise in inducing strong anti-tumor immune responses in preclinical models. Exosome vaccines can also be combined with immunostimulatory molecules such as adjuvants or cytokines to enhance immune activation. For example, exosomes loaded with IL-12 or GM-CSF can enhance the recruitment and activation of immune cells to promote a strong and sustained response. Currently, exosome vaccines carrying antigens from pathogens such as viral envelope proteins or bacterial toxins are being developed to fight infectious diseases. These vaccines can mimic pathogen structure and improve antigen presentation, providing a safer alternative to traditional vaccines. Looking ahead, exosome vaccines represent a promising direction for immunotherapy, providing innovative solutions for personalized medicine. Several ongoing studies and clinical trials are expected to realize their full potential, paving the way for safer and more effective vaccines against cancer and infectious diseases. References [1] Patrick Santos and Fausto Almeida, Frontiers in Immunology 2021 (doi: 10.3389/fimmu.2021.711565) [2] Min Deng et al., Asian Journal of Pharmaceutical Sciences 2023 (https://lnkd.in/eDiGG_q4) #Immunotherapy #ExosomeVaccines #CancerResearch #VaccineInnovation #Nanomedicine #BiomedicalInnovation #PrecisionMedicine #InfectiousDiseases #ExosomeTherapy #LifeSciences #OncologyBreakthroughs #ImmuneBoosting

The immunogenicity of lipid nanoparticle (LNP) formulations is a double-edged sword: while we aim to elicit strong immune responses to the encoded effective LNP-vaccines, we also seek to minimize reactogenicity driven by the LNP itself, which can cause adverse effects. Understanding which LNP components contribute to immunogenicity and reactogenicity is key to optimizing both efficacy and safety. A recent study reveals that adjusting PEG‑lipid length/ratio as well as replacing cholesterol and phospholipids in LNPs can enhance vaccine potency while reducing adverse reactions. It's a promising step toward safer, better‑tolerated mRNA‑LNP vaccine platforms. 🔍 Key Findings: 1. PEG‑lipids: Shortening PEG chains and lowering their molar ratio boosted antigen‑specific antibody responses and CD8⁺ T cell activity. 2. Cholesterol: Replacing cholesterol with plant sterols maintained strong immune responses while reducing inflammatory cytokines and side effects like fever. 3. Phospholipids: Swapping in phospholipids with different headgroups or tail structures achieved similar benefits—strong immunity, but less reactogenicity. 4. Expression‑response link: Higher in vivo protein expression in specific organs correlated positively with both stronger immune responses and more adverse reactions. ACS Nano. 2025 Jul 23. doi: 10.1021/acsnano.5c10648.

Latest on Lipid Nanoparticles (LNPs) and Endosomal Escape اخر المستجدات في طرق استخدام جزيئات النانو الدهنية RNA-LNP-based therapies and vaccines rely heavily on the effective delivery of RNA into the cytosol of target cells. تعتمد العلاجات واللقاحات المعتمدة على RNA-LNP بشكل كبير على التوصيل الفعال للحمض النووي الريبي (RNA) إلى السايتوبلازم داخل الخلية However, once these RNA-LNPs are taken up by the cells, they often become trapped within endosomes. بمجرد أن تمتص الخلايا هذه الـ جزيئات النانو، فإنها غالبًا ما تصبح محاصرة داخل الإندوسومات For the therapy to work, it is crucial that the RNA-LNPs escape the endosome into the cytoplasm. لكي ينجح العلاج، من الضروري أن تهرب RNA-LNPs من الإندوسوم إلى السيتوبلازم If they do not, the cells will return these RNA-LNPs outside the cell before they have a chance to release the RNA. إذا لم يحدث ذلك، فسوف تقوم الخلايا بإرجاع RNA-LNPs خارج الخلايا قبل أن تتاح لها فرصة إطلاق RNA. This is where the term "endosomal escape" comes into play. So, have scientists developed smart strategies to address this issue? فهل طور العلماء استراتيجيات ذكية لمعالجة هذه المشكلة؟ Absolutely! Many successful strategies have emerged, including the use of cationic lipids, polymers, and peptides. نعم! وقد ظهرت العديد من الاستراتيجيات الناجحة، بما في ذلك استخدام الدهون، والبوليمرات، والببتيدات. However, many of these approaches can be significantly toxic to cells or rely on non-biodegradable materials. ومع ذلك، فإن العديد من هذه الأساليب يمكن أن تكون سامة بشكل كبير للخلايا أو تعتمد على مواد غير قابلة للتحلل. Today, I want to highlight the use of acid-sensitive lipids in LNP formulations for endosomal escape. اليوم، أريد تسليط الضوء على استخدام الدهون الحساسة للأحماض في تركيبات LNP للهروب من الاندوسوم. **Why acid-sensitive lipids?** لماذ الدهون الحساسة للبيئة الحمضيه؟ Endosomes operate in a low pH environment, approximately pH 4.5. لأن تعمل الإندوسومات في بيئة ذات درجة حموضة منخفضة، حوالي 4.5 درجة حموضة. There are numerous examples of this approach, and I’d like to share a recent publication from Nature Nanotechnology that was released yesterday (link in the comments). أشارككم منشورًا حديثًا من Nature Nanotechnology الذي تم إصداره بالأمس (الرابط في التعليقات) Key Findings: - Acid-degradable lipids:The researchers synthesized acid-degradable lipids composed of polyethylene glycol lipids, anionic lipids, and cationic lipids using an azido-acetal linker. - Rapid breakdown:The azido-acetal linker degrades the endosome within minutes via hydrolysis. - Enhanced delivery:The study demonstrated significantly improved mRNA delivery efficiency to hematopoietic stem and progenitor cells in vitro compared to conventional LNPs. - Successful in vivo results:In vivo studies showed successful delivery to major organs in mice, including the liver, lungs, spleen, and brain. This research provides a promising direction for developing more effective and safer LNPs.

🔬 A Must-Read Review on mRNA Medicines: Recent Advances in Chemical Modifications, Design, and Engineering This comprehensive and insightful review, recently published in Nano Research by Xiaowen Hou et al., is one of the best I’ve read on mRNA medicines. It provides a clear and detailed overview of how chemical modifications, sequence optimization, and next-generation engineering are shaping the future of mRNA therapeutics. 💡 Key Takeaways: 🔹 Chemical Modifications – Enhancing Stability, Boosting Expression & Reducing Immune Response ✔ Nucleoside Modifications – Replacing uridine (U) with Ψ (pseudouridine) and other analogs (m1A, m6A, m5C, mo5C, m5U, s2U, 5moU) ✔ 5′ Cap Enhancements – Cap 1, Cap 2 structures, and anti-reverse cap analogs (ARCAs) ✔ Poly(A) Tail Engineering – Optimizing tail length and incorporating m6A modifications 🔹 Sequence Optimization – Maximizing Stability & Expression ✔ Fine-tuning UTRs & ORF Engineering – Adjusting 5’ and 3’ UTRs and using synonymous codon substitutions ✔ AI-Powered mRNA Design – Tools like LinearDesign generate ultra-stable mRNA in just 11 minutes, boosting protein expression up to 128-fold 🔹 mRNA Engineering – Expanding Therapeutic Potential ✔ Circular RNA (circRNA) & Self-Amplifying RNA (saRNA) – Offering longer stability, higher efficiency, and lower doses for therapies ✔ Multitailed mRNA – Enabling controlled protein expression for precise therapeutic applications 🚀 Beyond Vaccines – The Big Picture mRNA isn’t just for vaccines—it holds transformative potential in cancer immunotherapy, rare disease treatments, and beyond. The next big challenge? Refining stability, delivery, and expression control to bring these innovations from the lab to the clinic. ❓ What do you think is the biggest challenge for next-gen mRNA medicines? Let’s discuss! ⬇️ 📖 Find the full open-access paper in the comments below. 🔗 Follow me for insights on oligonucleotide synthesis, RNA therapeutics, and cutting-edge drug development. #mRNA #Biotech #DrugDevelopment #RNAtherapeutics #mRNAEngineering #SyntheticBiology