The IHNV virus has spread worldwide and is fatal to salmon and rainbow trout – costing millions in sales of lost farmed fish. The current vaccination approach requires needle injection of fish, one by one. Now, however, Seattle-based Lumen Bioscience has come up with a new technology to make recombinant vaccines in a type of blue-green algae called Spirulina that costs pennies to produce and can be fed to fish in their feed.
To be effective, oral vaccines have not only to survive the gut environment intact but must also target the appropriate gut-associated immune cells. The approach developed by Lumen overcomes many of the problems with complex and expensive encapsulation strategies attempted in the past, according to CEO Brian Finrow. ‘[It] focuses on a new oral-vaccine platform [using] engineered Spirulina to express high amounts of target antigen in a form that is both provocative to the immune system – ie generates a desirable immune response that protects against future infection – and can be ingested orally without purification, in an organism that has been used as a safe food source for both humans and fish for decades.’
While a handful of injectable vaccines against IHNV have been demonstrated in the lab, they remain commercially undeveloped, Finrow says. ‘A DNA vaccine delivered by injection encodes the ectodomain of the viral surface protein and has been variably effective in controlled settings, but is available commercially only in Canada. Nevertheless, it demonstrates that the “recombinant subunit” approach we are using is a viable one.’
To produce the new oral vaccine, the Lumen researchers first developed a strain of Spirulina that manufactures recombinant proteins in its cell walls that the salmon immune system recognises as IHNV viruses. They then rapidly grew the strain in a large-scale indoor production system – requiring only light, water, salt and trace nutrients – and harvested and dried all the raw Spirulina biomass. This dried powder can then be fed to the fish.
‘The dried Spirulina cells break open in the fish’s GI tract, releasing the vaccine “payload”, and from that point on the vaccine behaves like any other: it triggers an immune response that protects the fish from future IHNV attacks.’
Spirulina was selected for its safety, rapid growth and low cost, Finrow continues. ‘Unlike most algae, Spirulina is so robust it can be grown in enormous outdoor ponds for years without being taken over by bacteria or fungi that doomed most large-scale algae biofuel projects.’ In addition, he points out: ‘Spirulina cells love to make lots of protein. Spirulina naturally contains remarkably high levels of protein––as much as 70% of biomass when measured by dry weight––so it’s relatively easy to get the cells to make a lot of the vaccine protein inside their cell walls.’
Previous attempts to make vaccine in other production organisms have been thwarted because of their inability to produce commercially scalable amounts of protein, he notes. Before Lumen scientists invented the technology, he says, ‘no other group in the world was ever successful at engineering into Spirulina the kinds of complex genetic modifications needed to create an advanced vaccine like this. The group is also applying the technology to oral vaccines – including to protect people against malaria.