The project is spearheaded by Health Sciences Center professor Dr. David Peabody and assistant professor Dr. Bryce Chackerian.
Typically, vaccinations involve injecting someone with a harmless version of the virus, teaching their body to recognize and quickly destroy that virus. Instead, this new strategy employs proteins that simply look like a virus, termed virus-like particles, which can be attached to molecules that the body wouldn’t normally identify as a threat.
Using this system, Chackerian said the research team believes it can teach the body’s immune system to attack almost anything.
“The immune system responds really strongly to (VLPs). And so basically our idea is to develop vaccines where we take a target that’s normally poorly immunogenic and we display them in a more immunogenic context – on the surface of a virus-like particle,” Chackerian said.
Many viruses are difficult to vaccinate against because they can mutate — like the flu, which has a different “version” of itself each year, making it hard for the body to identify, he said.
Yet this technique can target parts of the virus that are consistently kept the same, but which the body doesn’t typically recognize. Think of a mutating virus as a person who wears a different mask every day — if someone is trained to recognize that person by their face, they will not be able to identify them. However, if he or she learns to recognize them by their body, they can figure out who it is regardless of what their face looks like.
“What we’re trying to do is develop vaccines against targets that are particularly hard to develop vaccines using more traditional, conventional methods,” Chackerian said. “We basically try to look for the Achilles heels of different pathogens.”
The group has established a massive library of VLPs attached to random protein fragments. When looking to develop a vaccine, they simply screen the library for usable VLPs, with antibodies that the body naturally produces against that target, whether it’s a virus or something else, Peabody said.
“It allows us to make a vaccine based on nothing more than the information already present in a particular antibody,” Peabody said. “In other words, if you give us a monoclonal antibody that neutralizes a virus, for example, within a few weeks we can give you a vaccine for that virus.”
The team has already used this technology to develop a more advanced HPV vaccine, which they are working to get into clinical trials, and they are quickly targeting numerous other applications, Chackerian said.
The group has even developed a potential vaccination against high cholesterol levels, which they have recently begun testing in animal models. In this case, the immune system is trained to attack a molecule that occurs naturally in the body called PCSK9, which reduces the breakdown of bad cholesterol, or LDL.
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“Even though your body has these mechanisms of tolerance where you don’t normally make a response against yourself, you can overcome that by displaying targets on VLPs. So the idea is that we could potentially develop vaccines for chronic diseases by targeting self-molecules that are involved in disease,” Chackerian said.
Recently, reductions in PCSK9 have been identified to cause a decrease in the amount of LDL without affecting levels of “good” cholesterol, he said. While some therapeutic techniques targeting PCSK9 are already being tested, the group feels that their system may offer a better option.
“There are several good things about vaccines using our strategy as opposed to other vaccines. One is that they’re very cheap to make, so they’re made in E. coli and you can just make huge quantities of it, on a huge scale if you want,” said Dr. Kathryn Frietze, a researcher in Chackerian’s lab. “A second part is that you would not need that many doses — even as few as one dose might be enough to elicit a good immune response. A lot of vaccines require multiple injections, and so these potentially wouldn’t need that, depending on exactly what you’re targeting. And safety - there are other VLP type vaccines that are on the market and they appear to be really safe.”
Frietze, who is using VLPs to target everything from ovarian cancer to the Dengue virus, said she feels their library and screening system allows the team to quickly find targets that would usually be extremely difficult.
“We’re pulling a needle out of a haystack,” she said.
Lauren Topper is a freelance writer for the Daily Lobo. She can be reached at news@dailylobo.com or on Twitter @DailyLobo.
