deepseek-v3： a strong mixture-of-experts language model - http://pyoq.stayirie.com/afitqvr.html

As seen during the COVID-19 pandemic, bottlenecks can occur at various stages of the vaccine supply chain, including shortages of vaccine ingredients, packaging materials, and fill-and-finish facilities. Needle-free vaccines, however, could be the answer to solving many of these bottlenecks, as they are manufactured differently from traditional needle-based vaccines. Additionally, as can be seen with AstraZeneca’s nasal spray FluMist vaccine, which was approved in September 2024, needle-free vaccines can also be self-administered at home by patients or their caregivers, removing a significant burden in vaccine delivery. In this article, we explore the advantages of needle-free vaccines and look at some of the companies and research studies that have recently made headlines for the development of needle-free technologies. The advantages of needle-free vaccines The main advantages of needle-free vaccines are that they are more stable at non-refrigerated temperatures and are much easier to administer, simplifying their transportation and distribution; they can even be posted directly to people's houses and can be disposed of in a normal trash bin. Steve Damon, chief executive officer (CEO) of Micron Biomedical, a needle-free vaccine developer, explained: “This overcomes a great deal of infrastructure challenges related to cold chain during transport and storage as well as sharps waste and clinicians for administration,” explained Damon. “In fact, data published in the Lancet reflects positive data during self-administration. Since the technology makes drugs easier to store for longer periods, the technology has also been recognized for stockpile vaccines.” Damon also stated that in developed countries like the U.S. and Europe, access to therapies and vaccines can be hindered due to provider shortages, needle phobia, and social determinants of health such as transportation, job flexibility, and child care needed to get to appointments. “This includes routine flu vaccines that might be more accessible if they were mailed home and self-administered and medications for conditions like obesity and pain, for which people may be motivated to treat but uncomfortable with an injection.” Micron Biomedical secures over $33 million for its dissolvable microarrays vaccine Micron Biomedical is working on developing the world’s first needle-free technology for drugs and vaccines that is based on dissolvable microarrays. According to Damon, this technology essentially looks like a button on a bandaid that, when pushed, delivers a thermostable vaccine or therapeutic directly into the uppermost layers of skin – above the body’s pain sensors – within moments. The drug then dissolves into the skin and the technology is peeled off and disposed of as non-sharp waste, able to be thrown in a regular trash bin, unlike needle-based vaccines. Micron’s team has had a lot to smile about recently. Last year, the Lancet recognized the company’s needle-free technology as potentially “game-changing” in humanitarian settings. This was mentioned during the publication of Micron’s positive measles and rubella phase 1/2 data from the first clinical trial of needle-free vaccines in children as young as nine months, as well as in adults, which demonstrated positive safety and immunogenicity results. Furthermore, so far this year, Micron has secured the following fundraisings for its technology: A $7.5 million grant from the Bill & Melinda Gates Foundation: This will support its efforts in increasing access to the measles-rubella vaccine and fund ongoing manufacturing scale-up efforts and activities to support a phase 2 trial in infants. A $3.7 million grant from the Coalition for Epidemic Preparedness Innovations (CEPI): This funding is intended to build on the learnings from the COVID-19 pandemic and will support Micron’s work on a needle-free version of a next-generation vaccine platform that can quickly be adapted to protect against pathogens that could emerge as potential pandemics, referred to as “Disease X”. A $2 million prize fund from the Biomedical Advanced Research and Development Authority (BARDA) Patch Forward competition: The money from this is intended to advance Micron’s work to co-develop needle-free versions of mRNA based broadly-protecting influenza vaccines with Zipcode Bio. A series A3 financing of more than $16 million: This is an extension of the company’s series A round and brings the total series A equity raise to more than $33 million. J2 Ventures, a fund with a track record for funding innovations that improve the health of the military, and the Global Health Investment Corporation (GHIC) led the round, which will expand commercial manufacturing of Micron’s technology. This flurry of financing for Micron’s technology really puts a spotlight on just how attractive the idea of needle-free vaccines is right now, particularly when it comes to dissolvable microarray vaccines – a technology yet to be approved by regulators. Damon said that Micron is now preparing and building its phase 3 and commercial manufacturing lines. He also mentioned that the company’s technology is being studied beyond vaccines, in other therapies that are currently injected, such as for obesity and diabetes. “Imagine medications to treat obesity, diabetes, pain, and women’s health that can be mailed to homes and self-administered without pain, without a clinician, and disposed of as non-sharps waste, in a regular trash bin. The access to therapeutics can overcome barriers in access, as well as offer more options to meet the preferences of patients.” Vaxxas advances needle-free mRNA vaccine program Australian company Vaxxas is working on a high-density microarray patch vaccine technology, which was initially developed at The University of Queensland before Vaxxas was established as a startup in 2011 by the university’s commercialization group UniQuest. The microarray patch is comprised of thousands of microscopic projections molded into a small patch. Each microprojection is ‘printed’ with a small dose of vaccine in a dried formulation and, when applied to the skin, the patch delivers the vaccine to the abundant immune cells that naturally reside immediately below the skin surface. It has already proven to be safe and tolerable in hundreds of trial participants and has been shown to induce equal or greater immune responses to injected vaccines at lower doses. In September 2024, Vaxxas announced that it had initiated a phase 1 clinical trial of a vaccine against pre-pandemic avian influenza strain H7N9 using its microarray patch technology. Conducted in collaboration with Australian clinical sites, the trial is being led by Vaxxas with oversight by BARDA. It is designed to expand foundational novel countermeasure capabilities in response to potential future pandemic threats to public health, as the recent uptick in bird flu cases is causing particular concern. More recently, in January 2025, Vaxxas was named a Concept Stage winner of BARDA’s Patch Forward Prize. As part of the initial Concept Stage, Vaxxas will receive $2 million from BARDA to accelerate its work advancing the company’s HD-MAP technology for the administration of a COVID-19 mRNA vaccine. The company also announced in January that CEPI had approved the progression of a $4.8 million program to develop heat-stable, dried-formulation mRNA vaccines delivered using Vaxxas’ patch. This approval follows promising results from Vaxxas’ preclinical work, including the expression of a seasonal influenza antigen that demonstrated dose-dependent immunogenicity of mRNA in lipid nanoparticles (LNPs) when delivered by Vaxxas’ needle-free technology. The studies also showed that once loaded onto the HD-MAP, the mRNA-LNPs could maintain stability at 2–8°C and 25°C for at least 12 months, and 40°C for at least one month. IntegriMedical’s needle-free technology attracts investment from Serum Institute of India In May 2024, the well-known Indian vaccine manufacturer, the Serum Institute of India (SII), announced plans to make a strategic investment in needle-free vaccine developer IntegriMedical, acquiring a stake of 20% to progress IntegriMedical’s needle-free injection system technology. The goal of the collaboration is to combine SII’s vaccine production and global supply expertise with IntegriMedical’s research capabilities and drug delivery technology. IntegriMedical’s technology is gaining momentum in India, after it received CDSCO approval in December 2022 and formally launched in the market in 2024. According to the company, the increase in sales since its launch indicated that healthcare professionals are choosing to recommend or switch to needle-free systems to accommodate children and patients who are scared of needles. The company’s needle-free injection system uses a high-pressured, spring-driven stainless-steel piston, dispensing medication uniformly in a consistent, predictable, spray-like pattern. Upon injection, a jet stream is produced, and medication is dispersed through a micro-orifice in the skin, reducing the pain and hazards of needles. The needle-free technology is in trials to compare its performance through immunogenicity assessments versus conventional hypodermic needles via a COVID-19 booster dose, and to investigate its safety, tolerability, and acceptability for administering a COVID-19 vaccine in children. Oxford researchers investigate vaccine delivery via ultrasound A recent study by researchers at the Institute of Biomedical Engineering in Oxford has also shown that ultrasound can be used as a needle-free vaccine delivery system, as it ‘pushes’ drugs through the skin, and could be more effective than conventional ‘needle and syringe’ delivery in eliciting an immune response. By using an effect called ‘cavitation’, which refers to the forming and collapsing of bubbles using sound waves, ultrasound can induce small movements in liquids, facilitating the transportation of medicines through barriers in the body – even through the skin. Doctoral student Darcy Dunn-Lawless, explained in the press release: “There are challenges around delivering a high enough dose via the skin. However, because the skin is a more immune-rich environment than the muscles which vaccines are traditionally injected into, we have found a lower dose delivered using ultrasound to the skin can still achieve a stronger immune response than one delivered via the traditional method”. The researchers’ initial tests showed 700 times fewer vaccine molecules were delivered by cavitation compared to injection, but that this method still produced a higher immune response.” The Oxford researchers combined ultrasound technology with DNA vectors to see if this approach could match the effectiveness of conventional ‘needle and syringe’ delivery in terms of the immune response. Findings suggest that using ultrasound in this way can successfully generate an immune reaction, eliciting a substantial antibody response. Given these findings, this ultrasound vaccine technique could end up becoming a viable option for delivering vaccines, and could perhaps soon be tested in clinical trials. What does the future hold for needle-free vaccines? According to an article published on Gavi’s – an international organization focused on vaccine development – website, while needle-free vaccines have the potential to transform immunization, more investment is needed to hasten their development to help protect against future pandemics. It points to microarray patches in particular, as the technology that can overcome logistical obstacles and mentions that the COVID-19 pandemic has reinvigorated interest and investment in the technology, which, as mentioned previously, has not yet been approved by regulators, despite being in development for several decades. There are still a number of challenges to overcome before the potential benefits of microarray patches can truly be realized. Because the vaccine in microarray patches is in a dry formulation, developers and manufacturers must ensure that enough of the antigen can be concentrated to actually deliver a full dose. Additionally, standardized quality control tests and sterility requirements for vaccine manufacturing must also be drawn up. Nevertheless, the needle-free vaccine field as a whole is looking very promising in terms of the progress companies are making. In addition to the successes of the companies mentioned in this article, there are other players in this space who are being vigilant in pushing forward their needle-free vaccines. PharmaJet, for one, which already has a U.S. Food and Drug Administration (FDA)-approved needle-free vaccine injector, signed a partnership agreement last year with Scancell to develop a needle-free DNA vaccine for advanced melanoma using PharmaJet’s delivery system, which had already shown effective uptake of the DNA vaccine in addition to offering speed, convenience, and enhanced patient experience. Meanwhile, the companies Crossject, Portal Instruments, NuGen Medical Devices, and Jurata Thin Film are working in this area, as well as big multinationals like AstraZeneca and Pfizer. Indeed, given the number of players in this space, the needle-free injector market size, which reached $15.6 billion in 2023, is projected to reach $43.4 billion by 2032, growing at a compound annual growth rate (CAGR) of 12.08%. According to an S&S Insider report, the market is growing rapidly along with the escalating requirements of pain-free drug delivery systems, greater needle-phobic population, increased vaccination drives, and the shift towards non-invasive healthcare solutions in varied geographies across the world. The future certainly looks bright for needle-free vaccines, as we wait and see whether microarray patches, in particular, will be approved for use, finally realizing their full potential.