Could silk microneedles make aquaculture vaccinations safer and more efficient?

Water-resistant microneedles made from food-grade silk could improve fish vaccination and help prevent disease outbreaks in aquaculture

Researchers at the Massachusetts Institute of Technology (MIT) have developed water-resistant silk microneedles that can deliver vaccines underwater to juvenile fish, potentially making aquaculture vaccination safer and more efficient.

Developed in collaboration with the U.S. Department of Agriculture (USDA), the technology uses food-grade silk microneedles coated with shellac, a resin used in food coatings and pills. The coating prevents the microneedles from dissolving prematurely in water, allowing them to penetrate fish skin, remain attached and release vaccines in a controlled manner before eventually degrading.

In a study published in ACS Nano, the researchers demonstrated that the microneedles could deliver different vaccine materials, including bacterin and DNA vaccines, underwater.

“Our approach could give farmers a more precise tool to maintain fish health,” said Benedetto Marelli, a professor in MIT’s Department of Civil and Environmental Engineering. “Farmers are really concerned about the health care of these fish, so providing them with better tools is really important.”

Vaccination is used to help prevent disease outbreaks in aquaculture, but existing methods present challenges. Vaccines administered through feed may not reach every fish, while immersion treatments require substantially larger quantities of treatment and are not completely effective.

Conventional vaccination with metal needles is currently considered the most effective vaccination method, but requires fish to be sedated, removed from the water and individually injected.

“Workers inject fish one by one,” said Meng Lin, an MIT postdoc and first author on the paper. “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.”

The MIT team adapted silk microneedle technology originally developed for delivering nutrients to plants. Earlier versions dissolved too quickly when exposed to water, releasing vaccines immediately and failing to penetrate fish skin.

To address this problem, the researchers applied 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 also preserved half of the DNA plasmids’ structure after four weeks of storage in dry conditions.

“That stability is important, particularly for the last mile of delivery, because aquaculture is mostly done in rural areas,” Marelli said. “This allows farmers to not need to rely on the infrastructure to maintain the cold chain.”

Breakthrough in fish mucosal immune system research could transform aquaculture vaccines

The researchers tested the technology in rainbow trout, demonstrating that the microneedles could deliver vaccines underwater to fish weighing as little as 1 to 2 grams.

Gregory Wiens, a researcher at the USDA’s National Center for Cool and Cold Water Aquaculture, said conventional needle-based vaccination isn’t well suited to rainbow trout until they reach approximately 30 grams.

“What our research shows is food-grade silk fibroin microneedles can deliver vaccines underwater to fish as small as 1 to 2 grams,” Wiens said. “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 said further development is needed before the technology can be 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 said. “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.”

Read the full study.

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