Exploiting a Very Small Achilles’ Heel

For the vast majority of bacteria, there is no life without iron. Unlike current vaccine and antibiotic technologies, which can be rendered useless by rapid gene mutation, Syntiron’s vaccine technology attacks at the most fundamental components required for survival.

The role of iron acquisition in bacteria is well supported in the scientific literature. Our core vaccine technology exploits the critical role of bacterial iron acquisition during infection and has proven effective at preventing infection in the following applications:

• Largescale field studies involving agricultural animals (E. coli, Salmonella spp., Pasteurella spp.)
• Laboratory studies involving animal models for human disease (Salmonella spp., Staphylococcus spp., Klebsiella pneumoniae, Campylobacter jejuni)

How it Works: The Iron Carrier

When iron is in short supply, bacteria develop specialized proteins that steal iron from the host. Pathogenic (disease-causing) bacteria require iron for growth and survival. But iron is also essential to animal hosts, which lock away iron using high-affinity soluble proteins such as heme and transferrin. Therefore, in order for bacteria to successfully invade and infect a host, they must utilize their own special iron-gathering protein systems to compete with the host for iron.

Specialized transport proteins called siderophore (siderophore is Greek for iron carrier) receptors are located on the outer surface of bacteria. Siderophore receptors belong to a class of tube-shaped proteins called Porins, which transport nutrients through the bacterial cell wall. Together, siderophore receptors and porins (SRPs) can be extracted from bacteria to form a purified protein vaccine.

It has long been recognized that iron transport proteins SRPs are highly conserved; in other words, many various bacterial species carry identical SRPs, even though the rest of their exterior structures (LPS, which determines serotype) are unique. This feature makes SRPs an attractive target for vaccine development, which has been recognized in scientific literature for many years.

Active immunization against SRPs results from disabling bacterial cell wall receptors required for acquisition of elemental iron— an essential bacterial nutrient for metabolism and survival in host animal tissues.

Environmental conditions, such as low iron availability, greatly influence bacterial protein expression during infection. Therefore, a vaccine to prevent infection should train the immune system to recognize the components that are expressed in that environment. Bacterial proteins such as siderophore receptors and transporters that are used to bring iron into the invading cell make ideal vaccine components because they are:

• required for survival
• important for infection
• similar among different strains of bacteria, which enables broad protection
• expressed on the surface of the bacteria, where the immune system can recognize them

Scientists at Epitopix first discovered an extraction technique to harvest SRP proteins from commercial scale bacterial fermentations. This made it possible to purify SRPs in quantities sufficient for economic vaccine production. Purified SRPs can be formulated with many common vaccine adjuvants for administration into a host population by injection.

Moving up the Food Chain: Safety and Efficacy in Humans

The critical proteins forming the basis of efficacy for this core technology in humans have been identified and are currently being further characterized by Syntiron’s research team.

Syntiron’s current vaccine development projects focus on three specific target areas associated with human bacterial infection:

• Nosocomial infection (hospital-acquired) infection (S. aureus)
• Foodborne illness (Salmonella spp., E. coli, Shigella spp.)
• Bioterrorism (Yersinia pestis, Bacillus anthracis, Burkholderia pseudomallei)