MIT engineers design a safer, more efficient vaccination system for farmed fish

Fish that are cultivated in pools or ponds are an increasingly important source of food around the world. Unfortunately, disease outbreaks can cause substantial losses in aquaculture. Fish farmers use vaccines to prevent disease outbreaks just like regular farmers, but vaccinating a fish is a lot harder than vaccinating a cow. The most effective way to vaccinate fish today uses needles, but there are several downsides to this process, both for the fish and the farmers. Now a team of researchers at MIT and the U.S. Department of Agriculture has developed a potentially better way to deliver vaccines. The approach uses water-resistant, food-grade microneedles that can lightly penetrate and remain attached to fish skin before decomposing. In a new paper published in ACS Nano, the researchers described their system and showed it could be used to deliver a range of cargos, such as bacterial vaccines.“To feed the world we need more fish, which are a major source of protein and nutrition,” says Benedetto Marelli, a professor in the Department of Civil and Environmental Engineering. “Aquaculture is a very effective way of producing a large amount of fish. Our approach could give farmers a more precise tool to maintain fish health. Farmers are really concerned about the health care of these fish, so providing them with better tools is really important.”Joining Marelli on the paper are Meng Li, an MIT postdoc and first author on the paper; Jad Raad MEng ’24; Yunteng Cao PhD ’22, a postdoc at Yale University; Yue Hu, a former MIT postdoc; Colleen Wolfe MEng ’23; Doyoon Kim, a former MIT postdoc; Bradley Frank, a current MIT postdoc; and Gregory Wiens, a researcher at the U.S. Department of Agriculture’s National Center for Cool and Cold Water Aquaculture.Better vaccine deliveryAquaculture holds enormous potential to address food insecurity, reduce energy consumption, and decarbonize global food systems. In 2021, for the first time, farmed aquatic animals exceeded wild-caught aquatic animals in global food production by weight.“The world’s population is going to grow by almost 2 billion people by 2050,” Marelli says. “Fish provide access to essential nutrition. They are high in protein and healthy fat, which are difficult to make, so the world is trying to produce more fish. But there are many challenges associated with fisheries.”To prevent losses to disease, farmers use a range of automated and manual vaccination strategies, each with their own drawbacks. Some treatments can go into fish food, but those might not reach every fish. Another method is putting the treatment directly in a pool and immersing the fish in the treated water. That approach requires far higher quantities of treatment and, again, isn’t 100 percent effective.The most effective way to vaccinate fish is with metal needles. The process requires farmers to sedate the fish, then get them out of the water and onto a conveyor belt, where workers hurry to vaccinate the fish and get them back in the water to minimize harm.“Workers inject fish one by one,” Li explains. “It’s high intensity, there’s a risk of cross contamination of blood-borne diseases, and workers may accidentally jab themselves because they are working so quickly. So it’s labor intensive, costly, stressful for fish, and dangerous for workers.”Marelli’s lab has been developing silk microneedles to deliver nutrients to plants for years. The silk has been classified as safe for human consumption in food coatings and can degrade in the body or in the environment over time.A few years ago, Marelli learned about the challenges with vaccinating fish at a conference in Southeast Asia, where aquaculture is an especially important part of the aquatic food supply. His lab received support from the Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) to explore adapting the silk platform he’d developed for underwater use for fish. But the early silk designs would quickly dissolve when exposed to water, releasing the vaccine immediately and failing to penetrate fish skin.Li, a biomedical engineer, started to work on the project in Marelli’s lab beginning in 2022. In 2024, she received a fellowship from the USDA, which provided funding as well as important connections with collaborators at the agency and beyond. For example, the U.S. Geological Survey gave the researchers access to a DNA vaccine for rainbow trout.Marelli credits Li with finding a way around silk’s tendency to soften when exposed to water. The system described in the new paper uses a thin layer of shellac, an insect-secreted resin used in food coating and pills, to make silk microneedles water-resistant by providing a moisture barrier that remains intact before fish injection.“The material choice is critical because we’re dealing with food, even though we expect the microneedle to fall out of the fish or to be degraded in their body,” Li says. “Our criteria were safety for fish and humans alike.”The researchers showed the microneedles can store a range of vaccines, and they demonstrated different versions of the microneedles that lasted longer in the water or diffused vaccines more quickly.“In some cases, you may want the vaccine released within 15 minutes, but in others, the release can last 10 or even 24 hours,” Li says. “That could be better for other therapeutic uses beyond vaccines.”The microneedles were also able to preserve half of the DNA plasmids’ structure when stored for four weeks in dry conditions.“That stability is important, particularly for the last mile of delivery, because aquaculture is mostly done in rural areas,” Marelli says. “This allows farmers to not need to rely on the infrastructure to maintain the cold chain.”Protecting fishJust like terrestrial animal vaccines, fish vaccines are most effective when administered early in life before disease exposure. That means the fish that farmers want to inject are small, further complicating vaccination. The researchers believe their approach could offer a better way to vaccinate small fish, and they tested it in rainbow trout.“In trout aquaculture, one of the biggest challenges we face is preventing disease early in a fish’s life, because traditional needle‑based vaccination just doesn’t work well until the fish reach about 30 grams, which leaves the smallest juveniles unprotected during a critical growth period,” says Wiens. “What our research shows is food‑grade silk fibroin microneedles can deliver vaccines underwater to fish as small as 1 to 2 grams. We designed these single‑use microneedles to pierce wet skin, stay attached while the fish swim, and release either bacterin or DNA vaccines in a controlled way.”The researchers say there is still work to be done before their device can be seamlessly used at scale in fish farms. But they believe this paper is an important first step.“We have all the components to believe this technology could be developed further,” Marelli says. “There are so many challenges with aquaculture and fish vaccination right now. We need to support farmers to operate safely, improve working conditions, protect their business, make vaccination more accessible, and improve the living conditions of farmed fish and ultimately the quality of the food we eat. This new technology could be a much more effective and safer approach.”The work was supported, in part, by MIT’s Abdul Latif Jameel Water and Food Systems Lab and the U.S. Department of Agriculture.