Constant Challenge for Discovery Propels Harvinder GillThe Texas Tech researcher has shown how vaccines can be administered more effectively through the use of creative methods of drug delivery.

Harvinder Gill is always looking for the next challenge.

Newswise — An associate professor in the Department of Chemical Engineering and the Whitacre Endowed Chair in Science and Engineering, Gill discovered early in his career that simply having a job, no matter how much it paid, was not going to be satisfactory. He entered the petroleum engineering industry shortly after earning his bachelor’s degree in chemical engineering, and a few years later even started his own manufacturing company.

But none of it was stimulating his innovative, exploratory side. So he harkened back to some things he had heard on his very first day as a chemical engineering undergraduate at Panjab University in Chandigarh, India.

“The professor comes in and asks if we know what chemical engineers do,” Gill said. “Obviously, I had no idea. So he comes in and talks about engineering and how chemical engineers helped make the first kidney dialysis machine and the first heart and lung machine. I thought, ‘OK, I could do something in medicine.’”

That small lecture proved to be the foundation for one of the top researchers at Texas Tech University, who is making breakthrough strides in the areas of drug and vaccine delivery and immunoengineering. His work is recognized worldwide and has landed him $8 million in grant funding while elevating the reputation of the research collective at Texas Tech.

Today, Gill and his research teams are making tremendous strides in the areas of using pollen grains and microneedles to deliver vaccines more efficiently, which could help prevent viruses from entering the body and reduce the instances of illness. It is work that provides him exactly what he seeks.

“There is great stimulation in the field of bioengineering,” Gill said. “There are always medical challenges and a need to improve. New ideas keep popping up in my head, and that keeps me going.”

Making pollen workThe skin acts as a tremendous deterrent to infectious pathogens. Unfortunately, the skin does not cover the entire human body.

The entry point for almost every viral or bacterial infection is the mucosal membranes – the nasal passages, mouth, rectum or sexual organs. Vaccines, on the other hand, are mostly delivered through an injection, giving us the necessary protection only after the pathogen has entered the body.

Gill, however, had a thought. What if the mucosal surfaces could be turned into another line of defense by applying vaccines directly to them, either in edible form or as nasal drops?

“That helps you induce a line of defense on the mucosal surface, which basically is in the form of antibodies in the mucosal secretions like saliva or mucus that is on the covering of these surfaces,” Gill said. “If you deliver a vaccine through the mucosal surface, you can generate antibodies in the mucus that can neutralize the pathogen and not let it get into the body. But to give a vaccine to the mucosal surface is hard. If you eat it, the body doesn’t care and will digest it in the stomach as if it was food, and the vaccine won’t reach tine intestine where it will have a beneficial impact as a vaccine. You have to engineer and come up with new ways to deliver vaccines to the mucosal surfaces.”

So Gill decided to transform the very curse that causes allergies for millions of people – the pollen grain – into a beneficial vaccine delivery system.

Not the whole pollen grain, but just the shell, which Gill said is mechanically durable and resistant to acidic digestion. The idea is to clean the shells of any ingredients, including, fats, proteins and other biomolecules, to where it is just a clean shell. Then, researchers can load the shells with vaccines to make edible microcapsules and deliver them to the intestinal mucosal surfaces where they can help stimulate the immune system and generate antibodies to form a protective barrier against viruses and bacteria.

Gill said the concept has been tested in mice with tremendously successful results.

“We have shown in the mouse models that the approach works and we can get a good mucosal immune response and also get antibody generation in the blood at the same time,” Gill said. “It works.”

Shrinking needlesRarely will you find anyone who loves getting a shot. For some, needles are a tremendous phobia that often prevents them from seeking care from a doctor for fear of having to be injected with a vaccine or drug of some kind.

In addition to the pollen grain, Gill and his researchers are exploring other ways of delivering vaccines, and one method they have developed is the use of microneedles.

Microneedles are microscopic projections on a patch that can be self-applied to the skin or even inside the mouth (adding to the desire to utilize mucosal surfaces) that can be coated with whatever vaccines are required. Microneedles are painless, require less of the prescribed antigen and they may not require a visit to a doctor’s office or hospital each time they are used, unlike a normal needle injection.

Gill said the microneedle method would be very advantageous in instances of allergy immunotherapy (allergy shots) where the patient is required to undergo a series of injections to control a specific allergy. By using microneedles, that process becomes much less painful and, theoretically, more effective.

“The results are very positive,” Gill said. “We have shown that the microneedles are comparable to the existing subcutaneous immunotherapy in their ability to prevent and actually treat allergies in a mouse model. It is really working and we are very excited. We wish to continue working on it and see where we can take it going forward, hopefully into clinics as soon as we can.”

Microneedles also could be used to help combat viruses and other illnesses for which there is no cure, such as HIV. Researchers know that when a person contracts HIV, it first goes into the stomach and intestines and creates a reservoir for the virus where it grows before being emitted into the rest of the body. Gill theorizes that by using microneedles to apply immunotherapy through the mouth, antibodies can be generated in the intestines and its mucus to prevent HIV from taking hold.

Gold standardContinuing on his idea of using mucosal surfaces for vaccine delivery, Gill is also making a universal influenza vaccine. But to make it, he has turned to gold.

Because the influenza virus changes at a rapid rate, it is difficult for scientists and doctors to keep up with the mutating strains, and the flu shot works only if the virus contained in the vaccine is the same as the virus that is circulating and making people ill. Gill said the World Health Organization and other agencies have to make the best, educated guess six months in advance of what will be the strain or strains of the virus that will circulate. Based on this guess, the seasonal vaccine is formulated each year.

Gill is using nanotechnology to make a ‘one-for-all’ universal influenza vaccine using gold nanoparticles. The vaccine can be given to nasal mucosa as a nasal drop. His team has shown that the vaccine can protect mice against different influenza strains including the 2009 H1N1 pandemic strain, and the H5N1 highly pathogenic avian influenza strain, which some scientists believe could be the next pandemic strain.

“We are very excited by the results,” Gill said. “We have recently found that the vaccine reduces viral load in ferrets if vaccinated ferrets are challenged with the 2009 H1N1 pandemic strain. So our vaccine works in mice and ferrets.”

Continued innovationGill considers himself a non-conventional thinker. He challenges existing paradigms and bridges gaps between different disciplines.

“The medical community is doing many treatments in patients as they were done decades ago.” Gill said. “There are actually many avenues of treatment and therapy that have not been considered, because people in one field are not aware of developments in another field. In fact, sometimes you have to think beyond the conventionally accepted norms.

“I tell my students to watch cartoons because in the world of cartoons anything is possible and you are free to think without limits.”

It is that avenue, the innovation surrounding future methods of drug and vaccine delivery, that plays right into Gill’s strengths in accepting and beating the next challenge ahead. His work has also elevated the stature of Texas Tech’s research as it continues to pursue Tier One status.

The Edward E. Whitacre Jr. College of Engineering continues to show its commitment to furthering research at Texas Tech through its facilities, such as the Maddox Engineering Research Center and the Experimental Sciences Building (ESB). Texas Tech also announced the groundbreaking later in February of an ESB II.

“Texas Tech has grown since I joined in terms of the ability for me and in general for other researchers to do great work,” Gill said. “The administration has made expenditures to help buy the equipment necessary for doing biomedical research and has helped to improve the animal research program.”

While he continues his work in biomedical engineering and immunotherapy, Gill is already looking ahead to his next challenge. As a graduate student at Georgia Institute of Technology, Gill wanted to work on tissue engineering before he delved into the field of drug delivery, and he’s never lost that passion for tissue engineering, attending a stem cell workshop when he first joined the Texas Tech faculty in 2009.

He has already begun working with stem cells to engineer tissue and sees himself becoming even more immersed in the field as it continues to grow.

“It is a very diverse field, so initially, we will see how it goes,” Gill said. “But we have some interesting results of making cardiomyocytes, the beating heart cells.

“There is great stimulation and there are always new ideas I keep coming up with, and that keeps me going.”

More information about Harvinder Gill and his research can be found at his website.