Innovative Techniques for Vaccine Development

A New Dawn in the Fight Against Viruses: Nature-Inspired Nanoparticles Offer Hope The COVID-19 pandemic has laid bare the urgent need for rapid development of tools to combat infectious diseases. This paper presents a promising new approach using nature-inspired nanoparticles as weapons in our arsenal against viral threats. Imagine a revolutionary vaccine, stable even without refrigeration, delivered effortlessly through a nasal spray. This is the vision of ADDoCoV, a key innovation presented in this research. This nanoparticle vaccine utilizes multiple copies of a crucial SARS-CoV-2 epitope, mimicking the natural structure of the virus and triggering potent immune responses. But the story doesn't end there. The researchers also developed Gigabody, a multivalent nanoparticle "superbinder" capable of neutralizing even the most elusive variants of the virus. This powerful tool holds immense potential for passive immunization, offering immediate protection to individuals exposed to the virus. The intricate interplay of synthetic, computational, and structural methods with in vitro and in vivo studies paints a picture of meticulous scientific rigor. The results are nothing short of inspiring: nanoparticles displaying remarkable stability, neutralizing antibodies cross-reacting with diverse viral strains, and a glimpse into a future where we can effectively combat respiratory viruses. This research not only provides a blueprint for crafting effective reagents against COVID-19 but also opens a new chapter in the development of next-generation vaccines and therapeutics. It ignites the imagination, leaving us to ponder the immense potential of harnessing nature's ingenuity to protect ourselves from the ever-evolving world of viruses. 📝 Article, Open Access https://lnkd.in/gMGDE8R2 📎 About License https://lnkd.in/gpbw3cEg 📦 PDBj EM Navigator https://lnkd.in/gjwRkgHs 📌 About Databank https://lnkd.in/gtGvwYtM Buzas D, Bunzel AH, Staufer O, Milodowski EJ, Edmunds GL, Bufton JC, Vidana Mateo BV, Yadav SKN, Gupta K, Fletcher C, Williamson MK, Harrison A, Borucu U, Capin J, Francis O, Balchin G, Hall S, Vega MV, Durbesson F, Lingappa S, Vincentelli R, Roe J, Wooldridge L, Burt R, Anderson RJL, Mulholland AJ, Hare J, Bailey M, Davidson AD, Finn A, Morgan D, Mann J, Spatz J, Garzoni F, Schaffitzel C, Berger I, (2023) Antibody Ther #disease #research #structuralbiology #merize

This excellent paper by Witeof et. al. describes studies documenting that an atomic-layer deposition processes applied to phage lambda and phage-like particle platform yield thermostable, single-shot vaccines. Quoting from the abstract: "Especially in developing countries, the impact of vaccines can be limited by logistical obstacles associated with multiple dose regimens, pathogen variants, and challenges imposed by requirements for maintaining vaccines at low temperatures during shipping and storage. Thus, there is a need for vaccines that can be flexibly modified to address evolving pathogen landscapes, are stable outside of narrow “cold-chain” temperatures and require administration of only single doses. Here we demonstrate in proof-of-concept studies a vaccine platform that addresses these impediments to more widespread use of vaccines. The platform relies on bacteriophage-derived phage-like-particles (PLPs) that utilize a “plug-and-play” antigen delivery system that allows for fast, easy alteration of antigens on the surface of the PLPs. Thermostability of PLP-based vaccines can be achieved by embedding the PLPs within glassy particles produced by spray drying, and nanoscopic aluminum oxide layers applied using atomic layer deposition (ALD) can serve to control release of antigen in vivo, yielding vaccine formulations that elicit strong immune responses after administration of single doses. Bacteriophage λ was stabilized by spray drying to form powders that were incubated at 37 °C for up to a year without loss of infectious activity. PLPs derived from bacteriophage λ were expressed and purified from E. coli cultures, and an in vitro conjugation strategy was used to decorate specific PLP surface sites with T4-lysozyme, a model vaccine antigen. The resulting T4-lysozyme:PLP complexes (Lys-PLPs) were embedded in glassy dry powders formed by spray drying and coated with nanometer-thick layers of alumina deposited by ALD in a fluidized bed reactor. Alumina-coated Lys-PLP vaccines were stable for a least a month at 50 °C, and single doses of the alumina-coated vaccines elicited immune responses that were indistinguishable from responses generated by conventional two-dose, prime-and-boost dosing regimens of alum-adjuvanted Lys-PLP vaccines."

Time for some extremely cool (and complex) microscopy techniques shedding light on self-amplifying mRNA vaccines Synthetic RNA vaccine platforms have gained unprecedented attention, primarily due to their rapid development, scalability, cost-effectiveness, and safety. A novel focus within this domain is the use of self-amplifying mRNA (SAM) vaccines which replicate within the cellular cytoplasm to induce a robust and prolonged immune response. These SAM molecules are delivered into cells via LNPs, which serve as protective and facilitating vehicles for cellular entry. In a pioneering study aimed at enhancing our understanding of how LNPs mediate the uptake and release of SAM into various cell types, researchers have delved into the cellular dynamics of SAM-LNP interaction within BHK-21 cells. Employing cutting-edge hyperspectral coherent anti-Stokes Raman scattering (HS-CARS) microscopy -a non-destructive chemical imaging technique of live cells based on the intrinsic vibrational contrast of its molecules- alongside multiphoton-excited fluorescence lifetime imaging microscopy (FLIM) -a technique that offers the ability to probe the cellular metabolic state-, the team has offered a detailed view into the intracellular behavior and expression of SAM post-delivery. Some highlights: 1) Notably, HS-CARS imaging highlighted increased lipid intensities in LNP-treated cells compared to controls, pointing to the successful cellular entry of LNPs. Furthermore, FLIM imaging provided evidence of SAM expression within both the nuclei and cytoplasm of BHK-21 cells, observable as early as 5 hours post-treatment. 2) An intriguing aspect of this study is the observed correlation between SAM expression and the mean fluorescence lifetime of NAD(P)H populations within cells. This finding suggests a potential link between the metabolic state of the cell and the activity of the delivered SAM, offering a novel avenue for understanding vaccine efficacy at the cellular level. This research, undoubtedly, underscores the utility of multimodal optical imaging techniques in unraveling the complex processes underlying LNP-mediated vaccine delivery and expression. By providing a clearer picture of how SAM-LNPs are taken up by cells and how they alter the cellular environment to facilitate vaccine expression, these insights pave the way for the development of more effective and targeted RNA vaccine formulations. If you want to learn more: https://lnkd.in/eQW-cGqa #nanotechnology #lnps #microscopy #biology #rna #vaccines #sam #nanomaterials #nanoparticles

In the ongoing quest to defeat #SARSCoV2, in 2020 Ingo Fricke and I designed an innovative alternative to the conventional #spike protein-focused #vaccines. Our approach targets a broader spectrum of viral #antigens which we believe can potentially lead to more robust and long-lasting immunity—particularly against #variants Our concept hinges on a #multipeptide vaccine, designed to target the virus at multiple points, thereby lessening the risk posed by viral mutations. Furthermore, we have incorporated a crucial aspect often overlooked in many vaccine strategies—the #mucosal immune response. Mucosal immunity plays a pivotal role in the body’s defense against respiratory viruses like SARS-CoV-2, and we believe that vaccines targeting this system can provide an essential line of defense. Preliminary data, as illustrated ahead, supports our hypothesis, giving us great hope for the potential of this “novel” approach. We’re encouraged by these results. Stay tuned for a detailed insight into our work and findings. https://osf.io/msu98/ Additionally, check out this insightful article where some initial data on this approach has been published. https://lnkd.in/ekX_9GRw #COVID19Research #VaccineDevelopment #MucosalImmunity #ScienceInnovation #NextGenVaccines