One of the most significant recent developments in vaccine technology has been the application of SRP technology. Previously, bacterin development was limited to the same tried and tested method:
- Isolate a pathogen of interest
- Grow it up in a laboratory and
- Add an adjuvant and put in a bottle.
SRP technology is part of a new approach to vaccines – subunit vaccines. Instead of taking the whole pathogen, key antigenic components are isolated and purified into a vaccine preparation. This allows much more targeted, selective immunity as opposed to the “shotgun approach” of a whole cell antigen system.
SRP is an abbreviation for siderophore receptor and porin proteins. They are specialized proteins involved in obtaining iron for bacterial function, and are crucial for survival in a limited iron environment. When bacteria are free living in the soil or in the gut, iron is readily available. Bacteria take iron in through normal transport systems to support physiologic functions. However, once bacteria invade the body of an animal or person, iron is always in a bound form – transferrin in the plasma, hemoglobin in red blood cells, etc – and thus in short supply.
In response to limited iron availability, bacterial genes turn on, producing and secreting siderophore proteins. These proteins have a high affinity for iron, in fact higher than most host proteins. Thus, the siderophores are able to “steal” iron from the mammalian host. At the same time, on the bacterial surface, other sets of genes turn on, producing abundant amounts of specialized transport proteins – siderophore receptors and porins. These proteins facilitate the transport of iron bound siderophores across the bacterial membrane, providing the bacteria with an iron source, even in an environment in which iron availability is extremely low.
Subunit vaccines utilizing SRP technology take advantage of the natural bacterial need for iron. SRP proteins are purified in the laboratory from bacteria grown in low iron conditions, the remaining non essential components of the bacteria are discarded, and the resultant bacterin contains only SRP proteins. The cow is vaccinated with this preparation, producing antibodies against the siderophore receptor proteins on the surface of the bacterial cell membrane. These antibodies attach to siderophore receptor sites, in essence blocking the transport of iron and depriving the bacterial cell of iron. Without iron to support crucial physiologic functions, the bacteria die. In addition, as with any other vaccine, antibodies opsonize the cell, bringing in other immune mechanisms to aid in combating the bacterial infection.
A commercial bacterin containing SRP proteins against Salmonella has been widely used in cattle, and has proven extremely effective in protecting against clinical illness and decreasing fecal shedding of bacterial organisms. Recently, a second product utilizing SRP technology has been conditionally licensed by the USDA to decrease fecal shedding of E. coli O157 as a pre-harvest food safety tool.
Many bacterial species utilize this siderophore receptor system to obtain iron from their environment. It is quite possible that the animal health industry may see additional products of this type in the future against a variety of bacterial diseases. On a broader note – as scientists learn more about physiology and function of pathogenic microorganisms, we can expect to see more types of products that take advantage of unique physiologic aspects of function rather than the standard model of vaccine development, which is to grow the whole organism up in the lab and put it in a bottle.