Breakthroughs in Global Health

Bob Garcea (left) gives Ted Randolph a vial of capsomeres, which Ted’s lab will turn into thermostable vaccine powder.
The human papillomavirus (HPV) vaccine was a landmark first in cancer prevention, protecting women against the virus that causes cervical cancers. Yet this life-saving vaccine and many others听remain inaccessible to a large part of the developing world due to their high cost and need for refrigeration. Many have tried to overcome these barriers to universal vaccination, but thus far, all听have fallen short.

Now BioFrontiers scientist Bob Garcea and collaborator, Ted Randolph, promise to finally听break down these barriers with a fresh, cross-disciplinary approach. Blending their expertise in听virology and chemical engineering, with a dash of ingenuity, they are redesigning low-cost, heat-stable vaccines with unprecedented success. Starting with HPV, their revolutionary vaccine designs听could transform vaccine programs worldwide to serve regions that need them most.

Virology Guru

Bob Garcea

Bob Garcea has been a transformative force in vaccine development since the 1980s. By studying viral structures, he has discovered new ways to simplify vaccines that drastically reduce their听cost and increase their reach. His discovery of virus-like particles (VLPs) led to听next-generation vaccines听that are more affordable and safer than traditional live-attenuated or heat-killed virus听vaccines, and have since become the new gold standard in vaccine design.

Now Bob promises to revolutionize vaccines once again with his discovery of viral capsomeres. 鈥淵ou don鈥檛 need the whole VLP to elicit an immune response,鈥 says Bob. 鈥淏uilding blocks of the听viral shell, termed capsomeres, are just as good at sensitizing the immune system against HPV.鈥 These capsomeres are so simple they can be churned out en masse by bacteria, whereas VLPs听require more complex biological production systems that are four times as costly. In addition, complex VLP vaccines are unstable, requiring liquid suspension and refrigeration for preservation.听Meanwhile, simple capsomeres are much more stable, lending themselves to a new heat-tolerant formulation. While Bob had no experience with vaccine formulations himself, he knew someone in a neighboring lab who did. 鈥淥ur BioFrontiers lab happened to be next to chemical engineers. They come at听problems in a very different way than we do. For them, it鈥檚 about practicality,鈥 says Bob. 鈥淚n particular, Ted Randolph had developed a technique for thermo-stabilizing proteins in powder form.鈥

Chemically Engineering Drug Formulations

Ted Randolph

Ted Randolph specializes in the practical matters of converting molecular discoveries into viable treatments. Biological proteins are notoriously unstable, particularly when exposed to heat. Ted鈥檚听job is to prevent them from degrading throughout the manufacture, storage, and distribution processes. The stakes are high鈥攁ny failures can compromise drug safety or efficacy, putting patients鈥櫶齦ives at risk.

鈥淢eeting the stringent requirements for chemical and conformational stability during shelf life is a daunting task,鈥 says Ted. Exploring how and why proteins go bad, he stabilizes them with听chemical engineering solutions. His cutting-edge technique to freeze-dry proteins into powder form has achieved unprecedented heat-stability, enduring temperatures as high as 120 degrees听Fahrenheit for 3 to 4 months.

鈥淲e brought our capsomeres over to Ted鈥檚 lab, and his team quickly made thermostable capsomere powders that equaled the ability of the current HPV vaccine to sensitize the immune system,鈥澨鼴ob says.

From Discovery to the Real-World

Recognizing the revolutionary nature of their breakthrough, and its potential to finally听overcome barriers to universal vaccination, the duo teamed up with Al Weimer of the Department of听Chemical and Biological Engineering in a unique collaboration that secured a $1.1 million grant from the Bill & Melinda Gates Foundation in 2016. The three investigators work in the Jennie Smoly听Caruthers Biotechnology Building (JSCBB) at 欧美口爆视频 Boulder, but their research areas have very different emphases, and the grant has helped them work together and collaborate to translate their听discovery into real-world vaccines. 鈥淚t鈥檚 really merging three different people with three different sets of expertise into one project,鈥 Garcea says. Ted adds, 鈥淭his formulation represents a听breakthrough technology previously unattainable for vaccines, allowing for safe and effective distribution wherever needed."

Bob and Ted also founded the spin-off company VitraVax Inc., turning to 欧美口爆视频鈥檚 Technology Transfer Office in conjunction with the Innovation Center of the Rockies to get up and running. Offering听essential guidance in identifying business drivers, finding equity support and licensing intellectual property, among other new challenges, these resources were instrumental in successfully听launching the new venture.

Impacting Global Health

With low-cost, heat-stable vaccines in a single dose, this BioFrontiers inspired team is aiming for the holy grail of vaccination. Their revolution in vaccine design would overcome the听barriers to universal vaccination and save millions of lives, particularly in developing nations.

Current disparities in access to HPV vaccination deprive millions听of women and men worldwide of this life-saving breakthrough in cancer prevention. 鈥淚n cancer, an ounce of prevention is worth a pound of cure,鈥 says Bob, explaining that HPV vaccination offers听
a more realistic strategy to save lives in areas without the resources for cervical cancer screening or treatments.

In addition, the team鈥檚 new techniqu

Ted Randolph (left) and Bob Garcea blend their expertise in virology and chemical engineering, creating low-cost, heat-stable vaccines.
e could lead to new, more protective HPV vaccines by lowering R&D costs. 鈥淎lthough a majority of HPV-related cancers result from HPV16 and听
18 infections, another 15 different strains can be oncogenic,鈥 Bob says. 鈥淥ur ability to fight this disease is currently limited听by manufacturing and distribution costs as well as the breadth听
of coverage.鈥

Beyond HPV, the team is laying the foundation for an entirely new paradigm in vaccinology that could impact all vaccines. 鈥淥ur decades of work aimed at better HPV vaccines may become more听about a process than a product鈥攁 way of making many types of vaccines rather than a single vaccine itself,鈥 Bob explains. With their听elegant combination of virology and chemical听engineering, Bob and Ted鈥檚 next-generation vaccines have the potential to rewrite the book on disease prevention worldwide. Their admirable work exemplifies the BioFrontiers mission to drive听medical advances through innovative cross-disciplinary science.


Denver Metro Chamber

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Each year these
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nds business听and civic leaders on the road for a two-day, one-night 鈥溑访揽诒悠 Experience鈥, connecting them to big ideas and communities in every corner of the state. As part of the May 2018 event, nearly three dozen 欧美口爆视频 Experience delegates听heard from leaders, faculty, postdoctoral fellows and IQ Biology graduate students,听in an afternoon packed with information about the interdisciplinary innovations happening at BioFrontiers.

2018 欧美口爆视频 Experience participants listen as Anastasia Karabina, a postdoctoral associate in the Leinwand Lab, describes the collaboration between BioFrontiers and Edgewise Therapeutics,a Boulder based start-up biotechnology company. Edgewise is focused on developing novel therapies for diseases involving skeletal muscle.