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Unlocking the dramatic health potential of DNA vaccines

Plasmids offer unique ability to trigger innate immunity in humans and animals, allowing for revolutionary performance and broadening the reach of vaccines to newborns and the developing world.

"The concept of DNA vaccines is fantastic," says Dr. Lorne Babiuk, director of VIDO.
Photo credit: Stuart Kasdorf for the U of S

A new type of vaccine is on the rise that holds unique potential to protect newborns, fight disease in the developing world and improve the power, longevity and efficiency of this long-standing health tool.

"DNA vaccines" are formulated with genetic sequences that trigger both innate and adaptive immune responses. They are easy and fast to multiply, safe and effective for newborns, do not require temperature-controlled 'cold chain' storage and carry potential to spur broad immunity to several threats at once.

"The concept of DNA vaccines is fantastic - it always has been," says Dr. Lorne Babiuk, director of the Vaccine and Infectious Disease Organization (VIDO) at the University of Saskatchewan. "If we can fully realize the potential of this type of vaccines, it will mean tremendous benefits for both animal and human health around the world."

Breaking down barriers

DNA vaccines consist of a circular piece of DNA, which contains immunity-inducing genetic sequences called CpG. The DNA acts as a vector to deliver the gene to the cell of an animal, where it 'turns on' an innate and a specific cellular immune response.

"In contrast to traditional vaccine delivery, whereby the whole organism or a protein from that organism is injected into the animal, we can now make the protein inside the body itself," says Babiuk. "So the proteins are made inside the animal and then the animals or human beings mount an immune response. It's a different type of immunization approach."

A key benefit of this approach is greater longevity and better quality control. "The theory is that because DNA stays in the body longer than most traditional vaccines, the immune response will last longer – this would be a very great advantage that would save producers time and money by avoiding re-vaccination," says Babiuk.

From a global perspective, probably the biggest advantage of DNA vaccines is the lack of a need for a cold chain, says Babiuk. "The need for a cold chain is a huge barrier for a lot of vaccines, especially in areas of the developing world where you don't have refrigeration. The ease of fermentation to increase the supply of these vaccines would be another huge advantage of DNA vaccines. Both advantages would greatly broaden the reach and availability of vaccines worldwide."

Among disease challenges particularly well suited to a DNA vaccine approach, protecting newborns is top of the list, says Babiuk.

"One of the greatest times of susceptibility to infection is almost immediately after birth. That's the same for any neonate, whether a child, piglet or calf. The fetus has been sitting in a warm, protected climate for quite an extended period of time. Then, all of a sudden, it enters the big world and faces hundreds of pathogens. It really is a total change in environment and the newborn is quite vulnerable."

Traditional vaccines are not given to newborns because of safety concerns related to introducing toxins or forms of pathogens at a vulnerable stage In addition, interference of maternal antibodies at this stage renders would weaken the effectiveness of vaccination. DNA vaccines, by inducing immunity at a cellular level, are able to bypass these hurdles.

"In cattle for example, we don't vaccinate calves for about six months after birth because of the interference of maternal antibodies," says Babiuk. "But with DNA vaccines we could immunize a calf as soon as it's dropped."

With the approach, cattlemen could theoretically prime the immunity of calves as soon as they are born, and then boost that immunity when the animals go to the feedlot. "That should give a very rapid response when they get in the feedlot," says Babiuk. To me, that's a very real advantage for the livestock industry."

Transfection hurdle

Graduate student Monika Polewicz is a member of VIDO's Neonatal Immunization program.
Photo credit: VIDO

But while the promise of DNA vaccines is great and researchers have made substantial progress in advancing this approach, to date only two DNA vaccines have been registered – one in fish and one in horses.

The major obstacle has been finding ways to efficiently introduce the foreign DNA into the cells of the animal – a process called transfection.

"The efficiency of transfection is the current bottleneck," says Babiuk. "You might put half a gram of DNA in the vaccine and 99.9 percent of that DNA never gets into the cell nucleus."

Improving efficiency of transfection has become a major research focus and scientists have succeeded in improving efficiency two fold. But there's still much greater improvement needed, says Babiuk.

One alternative approach proving attractive is a process of performing initial immunization with the DNA to prim the immune response, and then boosting the immunization with protein. "That approach is gaining a lot of traction," says Babiuk. "Basically, it sets up the immune system for a nice balanced response that's similar to natural infection."

With the transfection roadblock, an initial flurry of research interest from a variety of players has waned, but a number of strong efforts remain.

"When the interest in DNA vaccines started out, everybody wanted to be in it," says Babiuk. "As time went on and people realized it wouldn't be as simple as they hoped, some of the fly-by-nighters fell by the wayside. However there are a number of focused efforts that are continuing to work on it and they are the ones making headway. What has been lost in numbers has been made up for by the quality of commitment by these more serious groups."

Steady progress

Currently, VIDO's top priority in the area of DNA vaccines is formulation and delivery. "You can have the best vaccines in the world, but if you don't deliver them and formulate them properly you don't reach their full potential," says Babiuk.

Another priority area is food safety. "For example, we're pursuing an E. coli vaccine, which would further reduce the risk of transmission of E. coli to humans. We feel that's a novel and critical area that will reduce environmental contamination and further strengthen the image of the quality of beef.

"I think today beef is very safe and has a very good image, but as we all know it only takes a couple high profile incidences before people start questioning the safety of our food. That's why it's really important to continually make advances to ensure the quality of product the industry puts out remains top notch."

Complementing VIDO's DNA vaccine effort is the organization's research into "CpGs" – a type of bacterial DNA that elevates the body's normal disease resistance. VIDO researchers are investigating the potential to combine CpGs with vaccines for an even stronger immune response.

"With CpGs and other 'boosting compounds,' we're looking at enhancing innate immunity, which is the body's initial response to a danger signal," explains Babiuk. "For example, if there's a party with 20 people and one or two of them are sneezing and snorting, all of the people will be exposed to the pathogen, but maybe only 20 percent will actually come down with an infection. The reason is because the other 80 percent had a very rapid innate immune response, which cleared or stopped the infection in its tracks before it got established. We want to find ways to help the body ensure this type of strong response."

Of advantage to the livestock industry, CpGs and similar compounds have potential to replace or complement antibiotics. "This delivers benefits on a couple of levels. First, because there's a lot of pressure on the livestock industry to reduce antibiotic use. Secondly, because antibiotics are not 100 percent effective. If you can have synergy between the antibiotics and an innate immune response, you can have more effective results with reduced use of antibiotics.

"We're also looking at how these compounds could be used as a stand alone to protect animals from infection."

Getting the edge

VIDO's expanded facilities strengthen its standing as a leading centre for vaccine research, says Babiuk.
Photo credit: VIDO

The big players in DNA vaccines globally are relatively few, with the major pharmaceutical companies a handful of science organizations such as VIDO leading the way. There are also numerous small biotechnology companies, academic efforts and other specialized players helping to drive progress.

Few expect DNA vaccines to take off overnight, but steady progress and success will make this new type of vaccines more common over the next 10 to 15 years.

"Large companies are relatively conservative and if they already have a product that's registered, unless there's a really compelling reason, they don't want to go and register another product for the same syndrome," says Babiuk. "But people are always looking at marketing advantages. We're always looking at ways to get that edge and improve it an order of magnitude."

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