We are continually exposed to millions of microbes, parasites and toxins that would love to invade our bodies and cause disease. Considering the teeming microscopic life around us, it’s a wonder we usually manage to escape these microbial threats and the harmful infections they cause.
The reason, of course, is the remarkable protection mechanism inside our bodies called the immune system, a carefully designed network of cells, organs, and tissues that ward off pathogenic organisms. How the immune system can better battle the changing landscape of antibiotic-resistant microbial menaces is a question a community of scientists at U of T is facing.
The beauty of the immune system-and the pivotal function that researchers exploit-is its long-term memory. After it clears an infection, which generally takes about ten days, it stores a snapshot of the pathogen in case of future infections. This is termed the adaptive immune response. The next time the same pathogen enters the body, the immune system attacks and kills it much faster than the first time it infected the body.
While it is a robust defence against infections, like all biological systems, the immune system isn’t perfect and may take longer than it should to recognize a familiar pathogen. This can be especially dangerous if the pathogen causes serious, or fatal disease.
One way to ensure that our immune systems are primed and ready to fight a pathogenic invader is through bacterial vaccination. While human vaccines are more often designed to fight viruses, scientists have developed vaccines to stop bacterial pathogens in livestock and domestic animals for a near century. Human bacterial vaccines for diseases such as tetanus and diphtheria are a more recent development.
“The vaccine allows your immune system to take care of the pathogen. It’s like a wanted poster on a wall that says, ‘This is what we’re looking for and if you find it, don’t wait to see if it’s a good guy or not,'” said Dr. Scott Gray-Owen, professor of microbiology and molecular biology at U of T.
There are two kinds of bacterial vaccines. Acellular bacterial vaccines consist of two or more antigens, which are specific proteins or sugars derived from the pathogen’s surface. Mixtures of these antigens will generate an adaptive immune response. Cellular vaccines consist of whole bacterium, either dead or genetically engineered to remove its ability to cause disease. Either vaccine will protect against the real thing.
An effective bacterial vaccine includes an antigen unique to the single pathogen, like a barcode for a microbe. This gives the immune system a glimpse of the bacterium, which it stores it in its memory, prepared for future invasion.
Finding these barcodes is a major challenge, however, because many bacteria evade the immune system by changing their antigen barcodes in a mini-evolutionary race call antigenic variation.
Gray-Owen studies two pathogenic bacteria, N. gonorrhoeae which causes gonorrhea and N. meningitidis, the leading cause of bacterial meningitis. Vaccines have yet to be developed against either disease.
“Neisseria gonorrhoeae is a master at antigenic variation. It changes its surface at such a high rate. N. meningitidis is also notorious for changing its barcode, which is a sugar capsule located on its surface,” said Gray-Owen.
“There have been many attempts to find a single protein or other antigen that is conserved among all N. meningitidis or N. gonorrhoeae strains with no success so far. We are now trying to find small regions on various proteins that are conserved and then focus the immune response on these,” explained Gray-Owen.
Scientists are also racing to develop a vaccine for S. aureus, the most common cause of infections acquired in hospitals.
“S. aureus is very well adapted for growth in the blood. It colonizes areas of tissue disruption, where the normal protective barrier of the skin is disrupted, such as occurs in surgery,” explains Dr. Martin McGavin, professor of laboratory medicine and pathobiology at U of T.
Since S. aurerus appears to be evolving rapidly into strains that are resistant to antibiotics, it is becoming more of a problem for healthcare and a vaccine for S. aureus is increasingly important. As a result, pharmaceutical companies are reluctant to fund anti-biotic development against the pathogen, especially when bacterial resistance rapidly follows.
Advances in proteomic techniques, combined with the availability of genome sequence data, have helped scientists tackle the problem of antigenic variation. These tools allow scientists to identify the entire complement of proteins that are expressed on the surface of a bacterium. Any one of these proteins, or even a piece of one, may be a potential vaccine antigen.
