A CONVERSATION WITH ROBERT GARCEA, MD

Cervical cancer is directly related to prior infection with human papillomavirus (HPV). Primarily due to PAP screening, the rate of cervical cancer in the United States hasdropped dramatically, and is anticipated to decrease further in the next 20 years due to HPV vaccination. However, cervical cancer rates are high in the developing world, where both screening and vaccination are inaccessible. The lab of Robert Garcea, MD, is working to design next-generation HPV vaccines that increase access to vaccination. Here C3 talks with Dr. Garcea about his work and about how chance collaborations facilitated by the BioFrontiers Institute’s focus on breaking down the silos of academia are helping Dr. Garcea lead a sea change in the way we design and deliver vaccines of all sorts.

C3: The current HPV vaccine costs about $350 for two doses, making it inaccessible for many people around the world, including people without health insurance here in the U.S. How is your work bringing the cost down?

Garcea: In the 1980s, we described what are now called virus-like particles or VLPs, but we never thought about making vaccines from them – at the time, most vaccines were made from live or inactivated viruses. Now VLPs are the basis for the current HPV vaccine and several others. But subsequently we also discovered that you don’t need the whole VLP – the building blocks termed capsomeres [subunits of the viral shell] were just as good at sensitizing the immune system against HPV. The important part is that it’s significantly less expensive to manufacture capsomeres than it is to manufacture VLPs – perhaps a quarter of the manufacturing cost of current methods. In cancer, an ounce of prevention is worth a pound of cure. Better access to vaccines would keep people in developing countries from needing treatments that are simply not realistic.

C3: But it turns out that cost is only one of the barriers to vaccine use in developing countries…

Garcea: Sure, in addition to cost there’s refrigeration. Most vaccines are suspended in a liquid and they have to be kept cold. This formulation just isn’t practical for use in many developing countries. When my lab moved into the Jennie Smoly Caruthers Building, as part of the Boulder Campus’s new BioFrontiers Institute, our lab happened to be in a hallway next to chemical engineers, and we soon found they come at problems in a completely different way than we do. For them, it’s about practicality. In particular, Prof. Ted Randolph had developed a technique for ‘thermostabilizing’ proteins in a matrix of sugars. Basically,instead of suspending proteins in a liquid, Ted’s lab could formulate them in a powder. And that powder didn’t require refrigeration. We were still working with capsomeres and when we brought them over to Ted’s lab, his team was able to quickly make thermostable capsomere powders that equaled the ability of the current HPV vaccine to sensitize the immune system.

C3: In addition to cost and refrigeration, you’ve been studying a third problem associated with vaccine use.

Garcea: Well, then we became acquainted with another chemical engineer, Prof. Al Weimer. Al had developed a technique for “atomic layer deposition,” which is a method to coat surfaces with single atomic layers of alum or aluminum oxide. “ALD” had been used in applications including fluorescent lighting, but alum is also an “adjuvant” commonly used in vaccines to activate the immune system. We thought, wouldn’t it be interesting to take our thermostable capsomere powders, coat them in precisely defined layers of alum, and then put on another layer of the capsomere protein?

C3: So you’re talking about multilayered vaccines?

Garcea: Along with cost and refrigeration, a third problem with vaccines is compliance – getting people to come back for their booster. Now we have two layers: One priming layer, then the coating of alum that dissociates over weeks or months, which eventually exposes the second layer of capsomere proteins. When we submitted a grant proposal to the Gates Foundation describing singleshot, thermostabilized, inexpensive HPV vaccines, they said, “Why just HPV?” So now we’re looking at expanding this technique to other vaccines as well.

C3: So HPV is just a start?

Garcea: Science isn’t necessarily linear. It’s hard to predict where this kind of thing will go. It may turn out that decades of work aimed at better HPV vaccines become more about a process than a product – a way of making many types of vaccines rather than a single vaccine itself. But the goal remains the same: Better access and more use of vaccines that prevent disease.

About the author: Garth Sundem

In addition to writing for the University of Colorado Cancer Center, Garth is the author of the books The Geeks' Guide to World Domination, Brain Candy, and Geek Logik. Contact him at garth.sundem [at] ucdenver.edu.

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