DNA  VACCINES:  WHEN  LESS  IS  MORE

MANILA, April 18, 2005
 (STAR) STAR SCIENCE By Celia Aurora T. Torres-Villanueva, Ph.D.  -  "Take two shots of DNA and call me in the morning…" It’s only a matter of time before we’ll be hearing this from our doctors. The age of molecular medicine is truly upon us. This article is about just one specific "molecular" technology that has applications in medicine – DNA vaccines.

What are DNA vaccines? Well, let’s start with what we mean by DNA. DNA stands for deoxyribonucleic acid. "Deoxy…what?!" You can see why we call DNA by its nickname rather than by its full name. But even without knowing its full name, you’ve no doubt met the term "DNA" before. As you may know, DNA is the genetic material of all living things on our planet. By genetic material, we mean that the biological traits that we can pass on to our offspring are encoded in our DNA. The biological information required so we can have curly hair, brown eyes, and brown skin are in our DNA. That is, unless you get a perm, wear contacts, and get a tan! But even if you get a perm, if your children inherit your DNA for straight hair, then they will still be born with straight hair, whether or not you had a perm when your child was conceived or while the mom was pregnant.

So now we know what DNA is, and we already know what vaccines are. DNA vaccines, then, are simply vaccines that have ONLY DNA. Yet, while having less, DNA vaccines do more.

Most of the vaccines that we have now are composed of whole germs, or microbes, that cause the disease that we want to vaccinate ourselves against. For example, if we don’t want to get the flu, caused by influenza viruses, then we’d get injected with the influenza virus. If we didn’t want to get measles, we’d get injected with the measles virus. But why don’t we get sick if we get injected with the actual germ or pathogen? Well, these germs are first weakened, or attenuated, sometimes even killed, before they’re injected into us. In that way, our body’s immune response will "see" the germ in its disarmed and harmless form and be able to recognize it so that the next time we "see" that germ in an actual naturally acquired infection, when the germ will be armed and harmful, our immune response already knows it’s the enemy and will fight it, thus protecting us from the disease. It’s like training an army (our immune response) with mock enemies in costume (the vaccine).

Not all the vaccines that we are getting are made of killed or weakened germs. Some are made up of only parts of germs. These are called subunit vaccines, and are made up of proteins of the germs we are vaccinating against. It’s possible to use subunit vaccines rather than whole vaccines because, in fact, our immune response doesn’t actually "see" germs in their entirety. Our immune response only sees parts of germs, generally just their proteins. It’s like seeing or looking for just the insignia of the enemy or color of their uniform, without looking at the face of the enemy itself. So when we get surface antigen protein (subunit) of hepatitis B virus as vaccine, we’re protected against the entire hepatitis B virus because our immune response, in attacking the protein which is attached to the virus, is pretty much attacking the virus itself.

The good thing about using killed or subunit vaccines is that you avoid complications arising from the supposedly harmless germ (in live attenuated vaccines) reverting back to its harmful self. The problem, though, with using just killed germs or just parts of germs, is that only one arm of our immune response gets activated.

You see, our immune response has two arms — the humoral response and the cellular response. You could think of the two as being analogous to the air force and the infantry of the army, respectively. The humoral response involves antibodies which act like missiles, attacking germs that they can attach to. The cellular response acts like the infantry in that cells of the immune response directly act on the germs, or the cells where the germs are hiding, such as in a viral infection.

Live attenuated viral vaccines can induce the cellular response because these live viruses infect cells and produce viral proteins, which the immune response can see. The immune response knows that these proteins don’t really belong to the cell, but are foreign, i.e. enemy (to our immune response, everything foreign is an enemy). Thus, the infected cell gets "flagged," that it has been occupied by the enemy, and the cellular response can now go in and destroy that cell, thereby controlling the infection (pretty much like bombing your own ammunition factories when the enemy has gained control of them).

Now, when the immune response encounters only killed germs or just parts of germs in the vaccine, only the humoral response gets activated. For viral diseases, this is bad news for it’s very important to activate the cellular response in order to hunt down viruses as they hide in infected cells, and to kill these infected cells before they produce more viruses.

DNA vaccines combine the best of both worlds. DNA vaccines act like subunit vaccines, in that they encode for only specific proteins without the entire germ, and are thus safe. However, unlike subunit vaccines, DNA vaccines act like live attenuated vaccines because the DNA gets into our cells, which then produce the proteins for the immune response to see. This way, the DNA vaccine is mimicking an actual viral infection, where the virus proteins get produced by the infected cell itself, thus marking the cell for destruction by our cellular immune response.

But that’s not the end of the story. Aside from being more effective than killed or subunit vaccines and safer than live vaccines, DNA vaccines are also cheaper and more stable. To produce DNA vaccines, we only need a basic and standard molecular biology lab, where we can grow the DNA vaccine in bacterial cultures, purify the DNA from the bacteria, then inject the DNA directly into the patient. No need for complex synthesis, coupling with carriers, or culture of germs, all of which are very expensive. DNA vaccines are also more stable than their other counterparts. In a tropical country like ours, where conventional vaccines need to be transported to far-flung barrios in a "cold chain," i.e. constantly kept cold in expensive thermos containers on ice or refrigerated, transporting DNA vaccines in your pocket is much more practical... and cheaper.

DNA vaccines are also greatly empowered by the technology of genetic engineering. There are no available vaccines for many, if not all of the tropical diseases that plague our poor country. Besides not being a good investment for multinational countries (which may be forced for humanitarian reasons to provide such vaccines free or at low prices), vaccines against malaria and dengue have not been developed due to the complexities of the germs that cause them. For reasons too complicated to get into here and now, genetic engineering and DNA vaccine technology can help address these problems.

Our lab at UP is currently doing research aimed at developing DNA vaccines for dengue and malaria. We’re years away from producing commercially available vaccines, but we’ve taken the first steps and are moving forward. So when your children or grandchildren get DNA when they come in for their shots, you’ll know what they’re getting, and why they’ll be better off than you and your old-fashioned types of vaccines!

Formerly, when religion was strong and science weak, men mistook magic for medicine; now, when science is strong and religion weak, men mistake medicine for magic. – Thomas Szasz, M.D.

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Celia Aurora T. Torres-Villanueva is currently an Associate Professor with the National Institute of Molecular Biology and Biotechnology, University of the Philippines, Diliman, and concurrently an Associate Dean of the College of Science of the same university. She obtained a B.S. degree in Molecular Biology and Biotechnology from the College of Science, University of the Philippines, Diliman (cum laude). She received her Ph.D. in Molecular Genetics and Microbiology from the University of Massachusetts Medical Center, Worcester, Massachusetts, USA where she worked on DNA vaccines with one of the pioneering inventors in this new technology, Dr. Harriet L. Robinson. She is currently doing research on DNA vaccines for malaria, dengue and hog cholera, developing DNA vaccine delivery methods for aquaculture, and she is also studying Kawasaki Disease. She is also a senior law student at the UP College of Law. She is married to Zeus Villanueva with whom she has three children, Himig Angelo, Katha Angelica and Likha Angelissa. Address questions via e-mail to celia.torres_villanueva@up.edu.ph.


Reported by: Sol Jose Vanzi

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