Protein-based vaccines inspired by brine shrimp

Protein-based pharmaceuticals offer the potential for remarkable new treatments for AIDS, cancer, blood disease, and myriad other health conditions, including vaccinations for some of the world’s most harmful viruses. In order to be practically viable, however, these proteins need a two-year shelf life. Unfortunately, proteins tend to clump up when they are stored, forming aggregates and losing their biological function. Enter the brine shrimp.

Scientists have discovered populations of brine shrimp that have survived as dehydrated eggs under the extreme climate conditions of Death Valley, Calif., for upwards of sixty years. Professor Ted Randolph, of the University of Colorado at Boulder (CU), has attempted to harness the preservation techniques nature employs with brine shrimp and other species to create more sustainable vaccines.

In laboratory tests with mice, Randolph and his team discovered that, while proteins and benzyl alcohol (added to prevent microbial infections) resulted in dead mice, adding sugars and surfactants to the mixture resulted in a viable solution. The sugar compounds that naturally occur in cells and which are added to these vaccines form glasses when dried. When the proteins assume a glassy state, they are not able to aggregate into clumps. The issue, however, lies in the fact that vaccines need adjuvants, compounds are added to vaccines to enhance the recipient’s immune response to the injected antigen. The adjuvants tend to aggregate when frozen, however, and are thus rendered ineffective.

To overcome this next hurdle, scientists at CU controlled adjuvant aggregation using glass-forming additives -- the glass is formed at an accelerated rate, such that the cells do not have sufficient time to aggregate. To assist in this process, the solution is subjected to liquid nitrogen to almost instantaneously form the glass. As a result of this procedure, the vaccine’s biological activity stays constant for up to twenty-eight weeks stored at forty degrees Celsius, and up to a year when stored at room temperature.

This improved shelf life enables vaccine storage in stockpiles at distribution centers, for example, a FedEx facility, so that vaccines may be delivered immediately in emergency situations. In the case of a bioterrorism attack, these stockpiles could provide immediate relief to a significant percentage of the effected population, without the substantial lag time needed for vaccine development and production. Furthermore, these same properties will make for significantly more efficacious vaccines for use in developing countries, where limited electricity makes it difficult to meet storage temperature requirements for existing vaccines.

The next issue in the line of obstacles facing Professor Randolph’s team is that the vaccine on which they have been working -- a vaccine for botulism -- cannot be tested on humans. Botulism is not currently active in any human populations and, thus, its efficacy cannot be tested (at least, not ethically). The lab results on mouse populations, however, are very encouraging. As Professor Randolph pointed out, “We now have the ability to protect against massive bioterrorism attacks...on populations of mice.” Yet, despite these hindrances, the information and results from these tests are encouraging. The laboratory will begin testing on a shipment of anthrax in the coming weeks, and the team also plans to expand its research to a ricin vaccine.