image: Dr. Andrea Ferrante, an immunologist at the University of Alaska Fairbanks' Institute of Arctic Biology hopes to unravel a molecular mystery of how vaccines work. view more
Credit: Andrea Ferrante
A treatment credited with saving about nine million lives a year worldwide and bringing major human diseases including smallpox, tetanus, whooping cough and polio under some degree of control is said to have begun with a milkmaid, a boy, a cow and a doctor about two hundred years ago.
Yet in all that time, the details of how the treatment actually works are still unclear.
Dr. Andrea Ferrante, a University of Alaska Fairbanks scientist, hopes to change that.
As the story goes, an English milkmaid told physician Edward Jenner that she would never get smallpox - a deadly disease and a leading cause of blindness - because she had had cowpox; a mild, uncommon illness in cattle that can spread to humans through sores on a cow's udder.
The milkmaid's reasoning - that infection with cowpox protected her from smallpox - was a common belief among dairy workers and Jenner is said to have tested their theory by doing something then that would never be allowed today.
Taking pus from a cowpox sore on the hand of a milkmaid, he put it into a scratch on the arm of a boy. Although the boy felt poorly for several days, he made a full recovery.
Next, Jenner took pus from a human smallpox sore and put that into the boy's arm. Just as the dairy workers would have predicted, the boy did not contract smallpox. The doctor repeated his test on more people and the results were always the same - they did not get sick. Jenner didn't know how infection or inoculation with cowpox prevented people from getting small pox; he knew only that it did.
The veracity of the milkmaid story aside, all vaccines developed since that time stem from similar observations that inoculation appears to confer resistance to infection.
"Neither Jonas Salk nor Albert Sabin, who developed polio vaccines, had a precise understanding of how those vaccines worked; they just knew that patients administered with the vaccine they developed had a far smaller chance of getting sick," said Andrea Ferrante, an immunologist at UAF's Institute of Arctic Biology.
Ferrante received a $1.6 million grant from the National Institutes of Health to study the specific molecular processes that govern how vaccines do what they do with an eye toward creating safer and more effective disease-specific vaccines.
To understand what Ferrante is studying and how vaccines work, it is helpful to look at how our bodies fight illnesses. When germs such as bacteria or viruses enter a body and multiply, they cause an infection. One of the "tools" used by our bodies to fight infections are special white blood cells called dendritic cells, which "swallow" and digest germs.
Bits of protein from the digested germ are pushed to the outer surface of the dendritic cell and attach to "docking stations" where they attract another kind of special white blood cell called T-cells.
"Scientists have very little understanding of how the dendritic cells "decide" which bits of a digested germ to push out and expose on their outer surface," said Ferrante. "We know that the immune system responds, but we don't know exactly why."
It is the attraction between those bits of germ proteins and the special T-cells that triggers a person's immune system response. And it is the body's "memory" of that response that enables the immune system to act faster and more robustly to specific germs in future infections.
"Vaccines simulate what happens during a normal infection, with the dendritic cells showing bits of weakened germs to T-cells, just without the fuss of getting sick," said Ferrante. "Thus it generates a memory that the immune system uses when the real germ comes along. It is like training the system to recognize the undesired guest."
Using test tubes, not people, Ferrante, two PhD candidates and two undergraduate students are designing experiments in which they change the cellular environment of dendritic cells to answer their questions.
"We want to be able to identify whether it is pH or enzymes or something else that controls which bits of digested protein are exposed and therefore whether there's an immune response," said Ferrante. "A significant number of infections like those from Ebola and Zika viruses have yet to be restrained by immunization and understanding this mechanism may enable more targeted and effective vaccine preparations for such illnesses."
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Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI118888. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
ADDITIONAL CONTACTS: Andrea Ferrante, University of Alaska Fairbanks, Institute of Arctic Biology, aferrante@alaska.edu, 907-474-591 6.