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 It might be small, but it packs a mighty punch. By cramming vaccines into microscopic containers that release their loads after a preset amount of time, we may have found a way to deliver a vaccine and a booster shot all in one injection. 
 
 Kevin McHugh at the Massachusetts Institute of Technology and his colleagues have come up with a way of making drug-carrying particles that allow multiple doses of a vaccine to be delivered over weeks or even months. 
 
 Until now, this has been out of reach. “Vaccines are notoriously unstable,” says McHugh, and they often don’t last long at body temperature. 
 
 To make the microparticles, McHugh filled silicon cube moulds with a polymer that’s already used in implants and other medical devices. These cubes – which measure just a few hundred micrometres on each side – are then filled with tiny amounts of vaccine before a lid is fitted and the whole thing is heated slightly to seal it. 
 
 The polymer breaks down when in contact with water, but you can extend the time it takes to degrade by altering the structure of the particles in the polymer. 
 
 Shrink to fit 
 
 McHugh and his team gave five mice a single injection of a mix of microparticles designed to release their contents at different times. Each was filled with a protein that stimulates a similar kind of immune response as vaccines. In tests, they found that the protein was released within the mice 9, 20 and 41 days after the injection, just as the team planned. 
 
 “This is a novel method for making microparticles,” says Moein Moghimi at Durham University, UK. It could make it possible to deliver a vaccine and a booster in one go – which would be particularly useful for delivering vaccines in the developing world, where it can be hard to make sure that people get the boosters required to give lasting protection. They’re already working on versions of the particles that can last for 100 or 200 days before releasing their contents. 
 
 But Moghimi says that, in their current form, these microparticles are still too big to inject in the same way that we normally inject vaccines – deep into the muscle. At the moment they can only be injected just below the skin. McHugh is already working working to halve the size of the particles so they can be injected into muscle. 
 
 The technology could eventually be used to create “omni-vaccines” that protect against a whole host of diseases in one shot, says Kevin McHugh. 
 
 Journal reference: Science, DOI: 10.1126/science.aaf7447 
 
 Read more: Lyme disease is set to explode and we still don’t have a vaccine; Refusing boys HPV vaccine saves the NHS cash but is bad science ||||| MIT engineers have invented a new 3-D fabrication method that can generate a novel type of drug-carrying particle that could allow multiple doses of a drug or vaccine to be delivered over an extended time period with just one injection. 
 
 The new microparticles resemble tiny coffee cups that can be filled with a drug or vaccine and then sealed with a lid. The particles are made of a biocompatible, FDA-approved polymer that can be designed to degrade at specific times, spilling out the contents of the “cup.” 
 
 “We are very excited about this work because, for the first time, we can create a library of tiny, encased vaccine particles, each programmed to release at a precise, predictable time, so that people could potentially receive a single injection that, in effect, would have multiple boosters already built into it. This could have a significant impact on patients everywhere, especially in the developing world where patient compliance is particularly poor,” says Robert Langer, the David H. Koch Institute Professor at MIT. 
 
 Langer and Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research, are the senior authors of the paper, which appears online in Science on Sept. 14. The paper’s lead authors are postdoc Kevin McHugh and former postdoc Thanh D. Nguyen, now an assistant professor of mechanical engineering at the University of Connecticut. 
 
 After the lids are deposited onto the cups, the particles are heated slightly to form a tight seal between the lids and cups. (Courtesy of the Langer lab) 
 
 Sealed cups 
 
 Langer’s lab began working on the new drug delivery particles as part of a project funded by the Bill and Melinda Gates Foundation, which was seeking a way to deliver multiple doses of a vaccine over a specified period of time with just one injection. That could allow babies in developing nations, who might not see a doctor very often, to get one injection after birth that would deliver all of the vaccines they would need during the first one or two years of life. 
 
 Langer has previously developed polymer particles with drugs embedded throughout the particle, allowing them to be gradually released over time. However, for this project, the researchers wanted to come up with a way to deliver short bursts of a drug at specific time intervals, to mimic the way a series of vaccines would be given. 
 
 To achieve their goal, they set out to develop a sealable polymer cup made from PLGA, a biocompatible polymer that has already been approved for use in medical devices such as implants, sutures, and prosthetic devices. PLGA can also be designed to degrade at different rates, allowing for the fabrication of multiple particles that release their contents at different times. 
 
 Conventional 3-D printing techniques proved unsuitable for the material and size that the researchers wanted, so they had to invent a new way to fabricate the cups, drawing inspiration from computer chip manufacturing. 
 
 Using photolithography, they created silicon molds for the cups and the lids. Large arrays of about 2,000 molds are fit onto a glass slide, and these molds are used to shape the PLGA cups (cubes with edge lengths of a few hundred microns) and lids. Once the array of polymer cups has been formed, the researchers employed a custom-built, automated dispensing system to fill each cup with a drug or vaccine. After the cups are filled, the lids are aligned and lowered onto each cup, and the system is heated slightly until the cup and lid fuse together, sealing the drug inside. 
 
 “Each layer is first fabricated on its own, and then they’re assembled together,” Jaklenec says. “Part of the novelty is really in how we align and seal the layers. In doing so we developed a new method that can make structures which current 3-D printing methods cannot. This new method called SEAL (StampEd Assembly of polymer Layers) can be used with any thermoplastic material and allows for fabrication of microstructures with complex geometries that could have broad applications, including injectable pulsatile drug delivery, pH sensors, and 3-D microfluidic devices.” 
 
 Leon Bellan, an assistant professor of mechanical engineering and biomedical engineering at Vanderbilt University, says the approach offers an impressive level of control for constructing 3-D microparticles. 
 
 “It’s a new take on a 3-D printing process, and an elegant solution to building macroscopic 3-D structures out of materials that are relevant for biomedical applications,” says Bellan, who was not involved in the research. 
 
 An automated dispensing system can be used to load drugs into the 3-D microparticles. (Courtesy of the Langer lab) 
 
 Long-term delivery 
 
 The molecular weight of the PLGA polymer and the structure of the polymer molecules’ “backbone” determine how fast the particles will degrade after injection. The degradation rate determines when the drug will be released. By injecting many particles that degrade at different rates, the researchers can generate a strong burst of drug or vaccine at predetermined time points. “In the developing world, that might be the difference between not getting vaccinated and receiving all of your vaccines in one shot,” McHugh says. 
 
 In mice, the researchers showed that particles release in sharp bursts, without prior leakage, at 9, 20, and 41 days after injection. They then tested particles filled with ovalbumin, a protein found in egg whites that is commonly used to experimentally stimulate an immune response. Using a combination of particles that released ovalbumin at 9 and 41 days after injection, they found that a single injection of these particles was able to induce a strong immune response that was comparable to that provoked by two conventional injections with double the dose. 
 
 The researchers have also designed particles that can degrade and release hundreds of days after injection. One challenge to developing long-term vaccines based on such particles, the researchers say, is making sure that the encapsulated drug or vaccine remains stable at body temperature for a long period before being released. They are now testing these delivery particles with a variety of drugs, including existing vaccines, such as inactivated polio vaccine, and new vaccines still in development. They are also working on strategies to stabilize the vaccines. 
 
 “The SEAL technique could provide a new platform that can create nearly any tiny, fillable object with nearly any material, which could provide unprecedented opportunities in manufacturing in medicine and other areas,” Langer says. These particles could also be useful for delivering drugs that have to be given on a regular basis, such as allergy shots, to minimize the number of injections. 
 
 Other authors on the paper are Allison Linehan, David Yang, Adam Behrens, Sviatlana Rose, Zachary Tochka, Stephanie Tzeng, James Norman, Aaron Anselmo, Xian Xu, Stephanie Tomasic, Matthew Taylor, Jennifer Lu, and Rohiverth Guarecuco. ||||| A new technique allowing drugs or vaccines to be encapsulated within tiny biodegradable particles could see an end booster jabs 
 
 New technology could allow multiple vaccines to be delivered in single jab 
 
 Multiple injections for vaccinations could become a thing of the past, according to scientists who have developed an approach for delivering many doses of different substances in just one jab. 
 
 The technology involves encapsulating drugs or vaccines within tiny particles made of biodegradable polymers. Depending on their makeup, these polymers break down at different points in time, releasing their contents into the body. 
 
 Researchers say the approach could allow multiple vaccines to be delivered at once and remove the need for booster jabs. It may also prove handy in treatments for allergies, diabetes and even cancer where multiple injections are needed. 
 
 Dissolvable patch offers radical pain-free alternative to flu injection, study finds Read more 
 
 Researchers say it could prove valuable in developing countries, potentially allowing all childhood vaccines and their boosters to be given in one shot. 
 
 “One of the main limitations there is access to vaccines and the fact that you have to come back several times in order to get immunity from the pathogen,” said Ana Jaklenec, co-author of the research from the Massachusetts Institute of Technology. “A child or a baby is usually seen once, sometime around the birth time by some sort of healthcare worker.” 
 
 Writing in the journal Science, Jaklenec and colleagues describe how they developed the novel technique using biodegradable polymers already approved for use in humans. 
 
 The process, they reveal, involves making tiny silicone moulds – rather like ice cube trays – into which the biodegradable polymers are pressed and removed to form an array of box-like structures, each about 400 micrometres across. These are then filled with the required drug or vaccine and allowed to dry. 
 
 A lid, made from the same polymer, is then lined up on top of each micro-box and the system is briefly heated to seal it and prevent the drug or vaccine from leaking out. 
 
 When injected into the body, the boxes remain sealed until the polymer disintegrates – an event which occurs rapidly, with the timing dependant on the makeup of the polymer itself. 
 
 “What’s novel here is that the sharpness of how quickly the drug releases from the particle and the fact there is no leakage at all from the particle until [then],” said Jaklenec. 
 
 To test the approach, the team injected mice with microparticles made from one of three different polymers, each filled with a fluorescent substance. Using imaging techniques, the fluorescent substance was seen to be released at about nine days, 20 days or 41 days, depending on the polymer used. 
 
 The team also produced microparticles filled with a polio vaccine and exposed them to an antibody test to see if the vaccine’s potency was affected by the heat sealing: no such problem was detected. 
 
 Finally, mice were injected with two sets of microparticles made from different polymers – one designed to break down after about one week and the other after about five weeks – with both containing a protein found in egg white. The animals’ immune response was tracked for 16 weeks. 
 
 
 
 The results reveal that the filled microparticles triggered a response greater than two regular injections of the same dose of protein spaced four weeks apart. Indeed, the response was on a par with that from two regular injections each with twice the dose – probably down to the microparticles themselves boosting the immune response. 
 
 Einstein-inspired Isobar vaccine cooling system wins UK James Dyson award Read more 
 
 The team say the approach could have myriad applications in medicine and beyond. “ You could use pH sensitive materials [or] you can fill with any type of drug, or therapeutic or sensing drug, so we think it has a lot more application than just vaccines,” said Jaklenec. 
 
 But, she added, challenges remain, not least that vaccines are normally stored in refrigerators: “[We] have to stabilise all of these vaccines in the body for a long period of time at elevated temperature,” she said. 
 
 
 
 Andrew Pollard, professor of paediatric infection and immunity at the University of Oxford, was optimistic, although he noted it was early days. 
 
 “Technologies which allow slow or timed release of a dose and thus reduce the ‘needle burden’ of an immunisation programme without compromising protection would be welcomed by healthcare workers, parents and their offspring,” he said. 
 
 
 
 David Goldblatt, professor of vaccinology and immunology at University College London, said the approach was sophisticated. 
 
 
 
 But, he warned, hurdles remain, noting that it removed the chance to modify vaccines between doses and that there was no way to adjust the timing of vaccine release after injection. “We prefer to avoid immunising when you might have an active viral infection,” he said. “[What happens] if a child has malaria on the day that the [vaccine dose] is released automatically?” 
 
 Nevertheless, he said, the approach could prove revolutionary in helping children in developing countries to receive adequate vaccination. “It could be a game changer for that,” he said. ||||| In the first results from tests on an experimental Ebola vaccine, researchers at the National Institute of Allergy and Infectious Diseases (NIAID) report for the first time Wednesday that the shot is safe and that it leads to an immune response among healthy volunteers. The vaccine, developed by the National Institutes of Health and GlaxoSmithKline, was tested in 20 participants in the US at the NIH Clinical Center in Bethesda. 
 
 “This tells us that this is kind of a positive signal about moving to the next stage,” says Dr. Anthony Fauci, director of NIAID. 
 
 MORE: We’re Getting Closer to Vaccines and Drugs for Ebola 
 
 The vaccine is meant to protect uninfected people from Ebola, and, if effective, would be tested next in populations in high-risk areas such as west Africa, where the outbreak is ongoing, to immunize them against the virus. It does not contain live Ebola virus, but does contain snippets of its protein coat, just enough to alert the immune system to produce antibodies and immune cells that can recognize and destroy any live viruses that people might eventually encounter. The pieces of Ebola protein are introduced to the body via another virus, one related to the common cold that infects chimps. 
 
 The shot was tested in two doses among 10 people each; it triggered antibodies and immune cells that in primate studies were enough to protect them against a challenge of Ebola up to 10 months later. Whether that’s also the case among people won’t be known until the vaccine is tested among thousands more in west Africa, including health care workers and family members of ill patients, who are most vulnerable to getting exposed to the virus. 
 
 Only two people reported brief fevers after getting vaccinated. 
 
 MORE: Here’s How the Ebola Vaccine Trial Is Doing 
 
 The vaccine is one of two that scientists are preparing to test in the outbreak zone beginning in early 2015. Another candidate uses an entirely different approach involving a live Ebola virus that has been crippled so it can’t reproduce once it infects a person. The advantage to that system is that it might launch a stronger and more robust immune response than the NIAID and GSK shot, which may require a boost after several months to maintain strong immune protection against Ebola. “At the end of the day, you don’t know which is the most effective until you test them, and that’s the point,” says Fauci.
– Potential good news for kids—and the parents who hate to watch them squirm when faced with a needle. Researchers at the Massachusetts Institute of Technology have developed a technology that could allow childhood vaccines—for everything from polio to measles, mumps, and rubella—to be combined into a single injection, reports the BBC. The idea is that one shot would inject microscopic capsules of vaccine into a person, and those capsules would be designed to break down and release their contents at different times, per the Science study. A simpler application would be to deliver one vaccine and its necessary booster shots at one time. In tests on mice, researchers were able to time the release of the booster doses to exactly nine, 20, and 41 days after the initial shot. The concept has not been tested in humans yet. "For the first time, we can create a library of tiny, encased vaccine particles, each programmed to release at a precise, predictable time, so that people could potentially receive a single injection that, in effect, would have multiple boosters already built into it," MIT's Robert Langer says in a release. In the developing world especially, this "might be the difference between not getting vaccinated and receiving all of your vaccines in one shot," adds study author Kevin McHugh, whose research was funded by the Bill and Melinda Gates Foundation. Much work remains: For one thing, scientists would need to figure out how to keep the doses, normally refrigerated, stable in a warm body, per the Guardian. They also are trying to further shrink the capsules so they can be injected directly into muscle, per New Scientist. (A vaccine for the common cold is in the works.)