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In light of President Obama’s declaration of “national emergency” imposed by the outbreak of the H1N1 virus, Surprising Science is setting this week aside to discuss the history and science of vaccines and their importance in battling viruses and diseases, including swine flu.
More than two millennia ago in China or India, someone noticed that people who suffered and recovered from certain diseases never became reinfected. In a leap of logic, the person who noticed the connection tried to prevent the disease by inoculating themselves (or perhaps someone else) with a bit of infected matter.
That idea, now called vaccination, bumbled along through history until 1796. That’s when an English physician named Edward Jenner noticed that milkmaids rarely got smallpox, though they often had blisters from cowpox, which they caught from their cows. Jenner thought that the cowpox might prevent the women from getting smallpox. To test his idea, he took some material from the cowpox blister of a milkmaid and inoculated 8-year-old James Phipps. Six weeks later, Jenner injected young Phipps with fluid from a smallpox sore; Phipps didn’t contract smallpox.
Over the next decades, smallpox vaccination spread, and it was a common practice by the end of the 19th century. Around that time, two more vaccines were developed—by Louis Pasteur—against anthrax and rabies. The 20th century would see the development of vaccines for more than a dozen other diseases, including polio, measles and tetanus.
Long after Jenner’s first discovery, biologists would discover how vaccines work to prime our immune systems to fight off infections:
Though the original smallpox vaccine used a related virus, cowpox, most vaccines use a weakened or dead form of whatever disease they’re meant to prevent. Some of these vaccines will also include a substance called an adjuvant that boosts the effectiveness of the vaccine. (Scientists figured out the workings of alum, one type of adjuvant, last year.)
When the vaccine is injected, a person's immune system recognizes it as a foreign substance. Immune cells called macrophages digest most of the foreign material, but they keep a portion to help the immune system remember it. These identifying molecules are called antigens, and macrophages present these antigens to white blood cells called lymphocytes (which come in two types: T cells and B cells) in the lymph nodes. A mild immune response occurs, and even after the vaccine material is destroyed, the immune system is primed for a future attack.
The next time that a microbe with those antigens enters the body, the lymphocytes are ready to quickly recognize the microbe as foreign. When that happens, B cells make antibodies that attack the invading microbe and mark it for destruction by macrophages. If the microbe does enter cells, T cells attack those infected cells and destroy them before the disease can multiply and spread. The microbe is defeated before it can get a foothold in the body, before the person gets sick.
Tomorrow—Vaccine Week, Day 2: Success Stories
Asel Sartbaeva was taking her young daughter to the doctor for her childhood vaccines—a ritual familiar to most new parents—when something caught her attention. The doctor took the vaccine out of the refrigerator and administered it immediately, while it was still cold.
“I asked, sort of naively, why shouldn’t we wait for it to warm up,” Sartbaeva recalls. “The doctor said ‘no, no, no if you let it warm up it will spoil.”
Most parents would leave it at that. But Sartbaeva is a materials scientist, and the properties of different things in the world are inherently interesting to her. She went home and Googled what vaccines are made of, and why they need to be kept cold. The answer, she discovered, is that most vaccines contain proteins that break down at room temperature. And she learned something more shocking too—keeping vaccines cold during transport through the developed world is so challenging that some 40 percent of all vaccine doses are ruined before they can be used.
“I was just appalled with the numbers of how many vaccines are wasted today,” she says.
So Sartbaeva, who is part of the chemistry department at the University of Bath, decided to do something about it. She’s spent the past three years developing a method of using silica—the base material for sand and glass—to create tiny “cages” around the vaccine proteins. The silica binds around the proteins, conforming to their shapes to create multiple layers of protection. The process, which was just published in the journal Scientific Reports, can keep the proteins intact at temperatures of up to 100 degrees Celsius. The proteins will also stay intact for up to three years at room temperature. Then, when the vaccines reach their destination, the silica cages can be washed off using a chemical process.
Sartbaeva and her team, who have named the process “ensilication,” hope it will save millions of dollars in refrigerated transport and in wasted vaccines. This could allow vaccines to reach places with a lack of infrastructure that makes refrigeration difficult.
“If we could reduce the cost, it would be a tremendous achievement,” she says. “And if we can safely deliver vaccines without refrigeration, than people who don’t have access to vaccines today will be able to get them.”
Sartbaeva and her team have tested the process on the tetanus toxoid, the protein used in the tetanus vaccine. They also tested it on two other proteins—horse hemoglobin and an enzyme from egg whites. The process works on protein-based vaccines, including all the common childhood vaccines, such as the DTaP (diphtheria, tetanus and pertussis), the MMR (measles, mumps and rubella) and the pneumococcal vaccine, which can prevent pneumonia, sepsis and meningitis. It does not work on the newer category of DNA vaccines, which are currently under investigation but not yet on the market.
The team has begun animal trials, the results of which will be published in a second paper.
The next step for Sartbaeva is to perfect a mechanical method for removing the silica from the vaccine proteins, making chemical washing unnecessary. They’re currently working on a method involving shaking the vaccine vigorously enough to break the silica’s covalent bonds. The material can then be filtered to separate the silica from the protein. They’ve been getting good results, Sartbaeva says, but they need to shorten the process from 20 minutes to 1 or 2 before it’s practical to use in a medical setting. They’re also actively looking for pharmaceutical companies to partner with.
For Sartbaeva, who has been working with silica for 15 years, seeing the process work has been enormously exciting but also nerve-wracking. Silica had never been used in this capacity, and each failure in the experimenting process filled Sartbaeva with self-doubt.
“When it didn’t work, I said ‘OK, maybe this is crazy, maybe I should stop,’” she says. “I think the hardest thing was really believing it would work.”