A sugar polymer found on the cell surface of multiple pathogens could be key to developing a broad-spectrum vaccine
Developing new vaccines to protect against diseases that plague humans is fraught with numerous challenges-one being that microbes tend to vary how they look on the surface to avoid being identified and destroyed by the immune system. However, researchers from Brigham and Women’s Hospital (BWH) have discovered a sugar polymer that is common on the cell surface of several pathogens. This common sugar molecule makes it a promising target for the development of a broad-spectrum vaccine that can protect against numerous deadly microbes expressing this sugar on their cell surface.
The study will appear online in Proceedings of the National Academy of Sciences the week of May 27, 2013.
The researchers report that the sugar, known as beta-1-6-linked poly-N-acetyl glucosamine, or PNAG, is made by more bacterial, fungal, and other microbial organisms than previously thought. According to the researchers, antibodies produced naturally by humans and animals do not offer complete protection against microbes that express PNAG on their cell surface because the natural antibodies kill these microbes poorly.
Given this, the researchers created vaccine-induced, non-human-derived antibodies that would respond to a synthetic form of PNAG; and these antibodies had the properties needed for killing microbes. The researchers also tested a human-derived antibody that was able to bind to both the natural and synthetic forms of PNAG and could also kill microbes producing PNAG.
When the researchers injected mice with these antibodies, they observed protection against local and systemic infections caused by several unrelated pathogens, such as Streptococcus pyogenes, the cause of strep throat; Streptococcus pneumoniae, the cause of deadly pneumonias in the young and the elderly; Listeria monocytogenes, a cause of potentially fatal food poisoning; Neisseria meningitidis serogroup B, a serious cause of meningitis; Candida albicans, a very difficult to treat fungal infection; and, most surprisingly, a very potent strain causing malaria in mice, a surrogate for the most serious form of human malaria known as cerebral malaria.
The researchers also found the PNAG polymer on the surface of microbes that cause gonorrhea, trichomoniasis, serious gastrointestinal infections and typhoid fever. Additionally, they detected PNAG material on bacteria in tissues of humans with infections such as otitis media (ear infections) and tuberculosis-an important finding since it is critical that PNAG be produced during infection in order for the antibodies to do their job of killing and eliminating infectious agents.
