Honeybees and shrimp are now getting vaccinated

People get vaccinated. Cats and dogs get vaccinated. Cows, fish and even koalas get vaccinated. In a shift in how researchers think about immune protection, invertebrates are now getting vaccinated, too.

The first vaccine for honeybees was given conditional approval by the U.S. Department of Agriculture three years ago and has started rolling out across farms in the United States and Canada. Last month at the World Vaccine Congress in Washington, D.C., the company behind that vaccine announced early results from tests of a potential vaccine for shrimp.

These developments could be big news for agriculture. The beekeeping industry is valued at more than $10 billion, with losses from disease and pests estimated to cost hundreds of millions of dollars each year. For shrimp aquaculture, valued at tens of billions, the costs from diseases may be several billion dollars. Boosting invertebrate immune systems could fend off such diseases while reducing the need for antibiotics, which can encourage antibiotic resistance.

But unlike people and other vertebrates, invertebrates don’t have an adaptive immune system. That’s the system vaccines typically harness to make antibodies that mark specific pathogens for destruction. Though invertebrates, like vertebrates, do possess innate immunity, this form of immunity hasn’t been widely considered as a vaccine target on its own. The innate immune system is typically less specific, mostly targets features found across broad classes of pathogens and does not recognize or remember pathogens in the same way as the adaptive immune system.

“For a long time, it was considered that it was impossible, like vaccination couldn’t happen,” said Erin Strait, veterinarian and chief scientific officer of Dalan Animal Health, the company behind the vaccines. “That, in recent years, has been proven to not be true.”

Over recent decades, it has become increasingly clear that the innate immune system has its own ways of creating immune memory. Scientists think this memory is achieved through epigenetic changes, modifications to DNA that don’t alter its genetic sequence, and that these epigenetic changes can be passed from one generation to the next. This is how the team at Dalan believes its invertebrate vaccines are working.

The existing honeybee vaccine is made from inactivated Paenibacillus larvae, a bacterial pathogen that causes American foulbrood, a disease that infects and kills larval honeybees. When the vaccine is fed to the queen and she reproduces, her offspring become more resistant to those bacteria, as well as a virus that bees get from varroa mites.

For the potential shrimp vaccine, inactivated bacteria — Dalan has not disclosed the type — are fed to a brood stock that reproduces to yield a new generation that inherits immunity. These shrimp offspring are born vaccinated.

In a proof-of-concept trial in the lab, vaccinated shrimp were exposed to Vibrio parahaemolyticus bacteria, whichcause early mortality syndrome, and another pathogen called white spot syndrome virus. For shrimp exposed to V. parahaemolyticus, vaccination increased survival from 27 percent to 48 percent. For shrimp exposed to the virus, vaccination increased survival from zero percent to 58 percent.

While traditional vaccines are specific to a single pathogen, the honeybee and shrimp vaccines appear to provide protection against multiple pathogens. In shrimp, this protection is specifically intended for pathogens that are different from the one used in the vaccine.

While a shrimp vaccine could be valuable, Arun Dhar, a crustacean infectious disease researcher at University of Arizona in Tucson, would like to see Dalan Animal Health report its data in a published paper before he comments on its promise. He has studied crustacean pathology for many years and is skeptical of potential vaccine candidates. “Field data would really indicate the true efficacy,” he says.

Dalan is moving toward field trials in Southeast Asia, starting in Indonesia, that could provide such data and lead to regulatory approval.

Other teams have been working on shrimp vaccines, too, but challenges have included a limited immune response among juvenile shrimp. Dalan avoids this issue by feeding the vaccine to adult shrimp that then pass immunity to their offspring.

If these vaccines prove successful, other invertebrate species could be candidates for vaccination as well, especially others used in agriculture. Applied entomologist Christopher Williams of Liverpool John Moores University suggests that vaccines against silkworm pathogens would be appealing. His work has showed that probiotic interventions might also protect against the pathogenic fungus Beauveria bassiana, which grows on silkworms, breaks down their cuticle and releases toxins, ultimately killing them.