Developing a Simple Epidemic-Ending Defense (SEED) System

The SEED system was designed to enable and facilitate decentralized production and administration of safe mucosal immunizations wherever they are needed, without special skills or equipment.

The SEED system encodes useful antigen proteins in the genome of bacteriophages (or phages) that can be used to infect food-making or probiotic bacteria. The infected bacterial cells redirect their resources to producing more of the phage and the useful antigens. The design enables self-assembly of a live viral (phage) vaccine vector, which may provide a more effective immune response. The phage will not infect animal cells and will not be able to revert or change to be able to do so.

Bacteriophages are viruses that only infect bacteria. They are a kind of parasite of bacteria and are not alive outside them. They are everywhere and greatly outnumber bacteria. We are all full of them! 

Phages are incredibly effective and have been called "perfect predators" of their bacterial "prey". Bacteria have ways to defend against them and the phages have countermoves. This dynamic equilibrium is going on all around (and in) us, and is why there are still bacteria around. The type of phages we use are lytic, meaning they do not incorporate their genome into that of the bacteria, but kill them, making holes in the bacterial cells so the newly produced phage particles burst out. 

Another example you may have heard of where "good viruses" can help against disease is that of phage therapy. With phage therapy, phages that specifically infect disease-causing bacteria are used to help those with otherwise untreatable (antimicrobial-resistant) infections. Unlike with SEED phages phages for phage therapy generally need to be produced in the disease-causing bacteria and carefully purified for safe use. 

GSD Bio works with phages that naturally and specifically infect food-making or probiotic bacteria. For example, lactic acid bacteria are used in food-making (cheese, yogurt, sauerkraut, etc). They can be grown in simple food ingredients. Because the SEED system involves no disease-causing or toxic components at any stage, none need be purified away. The "lysate" (broth of burst probiotic bacteria, phage, and desired antigens) can be ready to go as a mucosal vaccine. It can be produced and used onsite wherever on earth it is needed, without special skills, equipment, or facilities. All thanks to helpful bacteriophages!

When the sequence encoding a potentially useful protein antigen is identified, it can first be incorporated into the phage genome. The susceptible bacterial host is then infected with assembled phages. Newly made phages are sequence-verified and are tested in the SEED process (where additional bacterial cells are grown and infected) to make sure they are making the desired antigen protein. The confirmed phage prototype is then ready to stock and to send out for appropriate testing. Many billions of phage particles are produced in a small tube, and few phage particles are needed to make more in a new cycle, so a small volume can provide a tremendous amount of material for testing and for subsequent democratized vaccine production. The phages are extremely heat stable (at least 40 degrees Celsius) over long time periods (at least several months) in simple salts solution and can be dried onto paper, dramatically simplifying storage and distribution of prototypes.

A small portion of the appropriate, antigen-encoding bacteriophage prototype is added to bacterial (such as Lactococcus lactis) cells, which are easily available globally and can be grown simply in food ingredients. Infection and vaccine production occurs at ambient temperature. The resulting lysate is ready to be administered mucosally (oral, nasal, etc) as vaccine, without requiring purification or processing. If helpful, it can be stably incorporated into food, drink, spray, gel, etc, for administration. A portion can be saved and stored for seeding further production (the process can be repeated). The simplicity and affordability of production and administration makes the SEED system volume-scalable and versatile for many types of applications (many doses, bulk dosing, dosing frequency).