Marquet: Plasmid-DNA vaccines are much easier to manufacture. They are made in a circular DNA that is grown in bacteria. It is such an easy process compared to typical vaccines. The manufacture takes weeks versus many months. They are easy to characterize and easy to store. They have many advantages in terms of manufacturing and cost.
BioPharm: I understand that plasmid DNA vaccines can be developed faster than traditional vaccines. How much faster can they be developed, especially when it comes to production for pandemics? What can plasmid DNA vaccines offer in terms of manufacturing scale-up and development times?Marquet: Like I said before, we are talking weeks as compared to many months here. You are also talking about using technologies that are readily available—fermenters for bacterial fermentation that can be used very readily for this production. So there is really nothing new that needs to be put together for this production. Also, another great advantage is storage. These vaccines can be stored at room temperature because they can be lyophilized, so of course, that's a major advantage.
BioPharm: Are there particular challenges to formulating plasmid DNA vaccines? Are there safety concerns that are different from the safety concerns of traditional vaccines?
Marquet: In terms of safety concerns, none, really. FDA requires many studies for safety and they are extremely safe. The plasmid DNA vaccines do not integrate into the body so they are very safe. This is a major advantage. In terms of formulation, I think one of the challenges currently for DNA vaccines is really to make them better, to increase the protection, to make sure they work as well or better than traditional vaccines. Because of that, there are still many challenges in terms of formulation. The magic formulation hasn't been found yet.
BioPharm: What types of delivery systems are being developed for plasmid DNA vaccines? Are there challenges to delivering plasmid DNA vaccines to their targets in the body?
Marquet: Yes, absolutely; the main challenge is delivery. The delivery systems for DNA vaccines go from very simple, naked DNA—just a plasmid in the buffer. In some cases, lipids can be added, some polymers can be added, and also there are systems such as electroporation that are being used and tested at the clinical site right now.
BioPharm: There are no plasmid DNA vaccines on the market today. Are there any that are close to being approved?
Marquet: Interestingly, there are DNA vaccines for animals that are working on right now and are on the market. There is a DNA vaccine for salmon and there is a DNA vaccine for horses, and they work really well. In terms of DNA vaccines for human use, I think that there is a lot of hope and a lot of enthusiasm. Several of them are in advanced clinical trials but none of them have been approved yet.
BioPharm: Why are plasmid DNA vaccines sometimes used in conjunction with traditional subunit vaccines?
Marquet: The reason they're used in conjunction with other vaccines is really to increase efficacy, and clinical trials have shown that by using this method you get better protection, at least in animal studies. This is the reason why they are used in this manner.
BioPharm: After delivery, the plasmid exists independently in the host. Why isn't the plasmid killed off by the host's immune system?
Marquet: Well actually, the plasmid is killed by the human system. The way it works is: You deliver the plasmid DNA into the body, it gets into the cell, the protein is expressed, and then the plasmid is eventually destroyed by the host.
BioPharm: Have effectiveness studies been conducted? If so, how effective are plasmid DNA vaccines when compared to traditional vaccines?
Marquet: I think that plasmid DNA vaccines have a lot of advantages in terms of cost, manufacturing, the mechanism of action, which is very simple. But we haven't really found a way that is really optimal for protection in terms of DNA vaccines. But I think it is very hopeful because there are DNA vaccines that are working in some animal species and I think this is very encouraging.
Magda Marquet, PhD, co-CEO and co-president, Althea Technologies