Most thin strips that dissolve in the mouth deliver a burst of minty-freshness. But what if they could deliver life-saving vaccines?
This was the question posed to some exceptionally enterprising undergraduate students at Johns Hopkins University, and they have come surprisingly close to an answer.
The seven-student team tackled the problem of rotavirus, the most common cause of severe diarrhea in children under five, leading to approximately 600,000 deaths annually according to the World Health Organization.
While the European Medicines Agency and the U.S. Food and Drug Administration (FDA) approved two new rotavirus vaccines in 2006, they have yet to reach the millions of children in developing countries who need them most.
In just two semesters the students were able to develop a thin strip that could dissolve in a baby's mouth while allowing the vaccine to be released in just the right place to trigger an immune response.
The project came about when Dr. Vu Truong, co-founder of Aridis Pharmaceuticals, contacted a former colleague, Dr. Hai-Quan Mao, assistant professor of materials science and engineering at Johns Hopkins's Whiting School of Engineering.
Aridis, with funding from PATH and the Gates Foundation, already had vaccine stabilization technologies that allowed the company to create a dry, stable rotavirus vaccine at room temperatures. This vaccine has the prodigious advantage of not requiring refrigeration, making it cheaper and easier to transport and store, a key hurdle to disseminating medicine in the developing world.
And unlike the other two rotavirus vaccines, it is not administered as a liquid. The researchers know that giving any child a liquid can be a challenge. Kids love to spit things out which can raise questions about administering another expensive dose to ensure vaccination.
Aridis needed a novel delivery system, so Truong approached Mao knowing that he had the expertise in biomaterials. He specifically asked Mao to produce a product resembling a thin strip to deliver the room-temperature vaccine.
Mao recruited one of his undergraduate lab students, Christopher Yu, who became the co-leader of the challenge.
It turned into a challenge that the students embraced. The team put in hours far beyond the average campus lab time, working nights and weekends to tackle the two major problems in developing a viable thin strip.
The first obstacle was how to create the thin strip in the first place. While the commercial manufacturing process works fine if you're only delivering concentrated mint (or cinnamon, as some people prefer), the harsh solvents and high temperatures used to make strips would destroy the vaccine.
After extensive research and testing, Yu and his team were able to refine production and the drying process at room temperature to produce the strips.
Once the strips could be manufactured with the vaccine, there was another problem of coating the strips so the vaccine could survive the onslaught of acid in the stomach.
"The vaccine needs to remain active through the harsh environment of the stomach, where the acid can act on vaccine to destroy it," Truong said. "It needs to make it to the small intestine where the virus first acts on the immune system."
The students were able to identify an FDA-approved polymer coating that could protect the vaccine from stomach acid and allow it to release the medicine afterwards in the more pH-friendly environment of the small intestine.
"The most difficult part was probably designing the film and protective coating together," Yu said. "Making both aspects complement each other while being compatible was the trick."
With the challenge completed and commencement on the horizon, the students turned their product over to Aridis for testing. So far, the results are more than promising.
"The delivery vehicle has been successful in early studies. Not only room temperature, but it also showed that the vaccine is well protected in animal studies," Truong said.
The room-temperature vaccine has already made it through Phase II testing in infants, but with a new delivery mechanism, they will have to start again at Phase I. Truong and his team already know Aridis' vaccine has been successful thus far, so the biggest remaining question is if the active vaccine can sail through the treacherous stomach acids to unload on the shores of the small intestine.
If this vaccine does eventually make it through to an approval, it will be the third rotavirus vaccine on the market. But Truong is assured that three is not a crowd.
"If you look at the two vaccine on the market, both are not stable at room temperature, the Merck vaccine is liquid, so it will always be less stable than a dried temperature [vaccine]. And the GlaxoSmithKline product is freeze-dried that requires multiple steps to use, to reconstitute, to deliver as a liquid," Truong pointed out. "The cost of storing these vaccines is more than a lot of the vaccines they're making in the developing world."
Not only are these vaccines much more expensive than vaccines being produced in the developing world, Truong noted that these vaccines are more expensive to transport, store and administer than the actual cost of producing the vaccine in the U.S.
Truong hopes that Aridis' vaccine could hit the market in as few as six or seven years because the vaccine itself has already passed some Stage II trials, far less than the usual FDA approval time of nine to eleven years for vaccines.
For the students, they hope the success of the project will resonate far beyond the walls of Johns Hopkins. "If our delivery system makes it to market," Yu said, "I think it will have a high impact in world health - knowing that potential is definitely rewarding."
This article was reviewed by Dr. Manny Alvarez.