Human immunodeficiency virus, HIV, is responsible for the disease Aids. Every year, around 2 million people, including 250,000 children, die because they have become infected with the virus, with the vast majority of deaths occurring in sub-Saharan Africa. Efforts by the World Health Organisation and other aid agencies are beginning to reduce mortality levels. Nevertheless, HIV – which wreaks its havoc by attacking the very immune system that is supposed to protect humans against disease – is still destined to cause tens of millions of deaths over the coming decades before it is brought under control.
The notion that the virus could be used to improve human health is therefore an unexpected one. Nevertheless, this is the remarkable idea that is being pursued by Mary Collins, professor of immunology at University College London. She is leading a group of scientists who are devising ways to turn HIV’s lethal properties on their head and to harness the virus so that it can be used to treat a range of diseases.
Taming HIV and using it as the basis of treatments for medical conditions sounds a fairly dangerous proposal. HIV is a deadly virus after all…
The idea may sound alarming but there is a history of using viruses like HIV to treat people. Similar viruses have been used to tackle cases of immune deficiency diseases, for example. These diseases, such as SCID (severe combined immunodeficiency), affect children who inherit defective genes which prevent them from developing working immune systems. As a result, they cannot fight simple infections. SCID is often called the “boy in the bubble disease” after the case of David Vetter, a boy with the disease, who lived from 1971 to 1984 in a plastic, germ-free bubble.
However, scientists have recently learned how to engineer viruses like HIV so that they carry the gene that is missing in these children. Then you can take some of their bone marrow, where red and white blood cells are manufactured, and infect it with the engineered virus. The virus infects their cells, carrying in the missing gene which becomes incorporated in the DNA of these cells. Effectively, you have used the virus to change the genetic makeup of the patient’s marrow so that it can start to make white blood cells and so defend his or her body against diseases. These children can then live normal lives.
The trick is to use the techniques of genetic engineering to alter viruses so that they do good rather than harm. I am developing ways to take this technique a stage further – to use this engineered virus as a vaccine.
So how would this work?
In this case, you would use HIV that has been genetically engineered so that its ability to replicate has been curtailed. Essentially, you remove a great deal of the genetic material that these viruses use to grow and divide. That makes them safe to exploit.
However, the really important feature about HIV is that this is a virus that directly attacks a victim’s immune system. In particular, it targets dendritic cells and infiltrates them. These infected cells then pass on the virus to the lymph nodes and then to T-cells. And of course T-cells are critical to our ability to fight off infections and disease. They direct the body’s immune system. Thus, in the case of Aids, the HIV virus infects T-cells, kills them, and leaves patients’ bodies defenceless against opportunistic infections. The key point is that HIV lets you get directly to the linchpin of the body’s defence mechanisms, the T-cells.
What we are doing is exploiting the ability of HIV – disabled so that it lacks mechanisms to replicate – to home in on the body’s T-cells. We can then fit out the virus with proteins that belong to another virus, for example influenza.
What is the purpose of doing that?
The disabled HIV vaccine, carrying the flu proteins, will go straight to activate the body’s T-cells. When T-cells come across pieces of foreign protein in our bodies, they stimulate several different types of attack against these invaders. Defence cells called killer T-cells are let loose. So, by using HIV, we have a mechanism for controlling the behaviour of T-cells and for directing our defences against diseases that we are particularly keen to protect people from.
We have only done this with mice at present, I should make clear. But it has worked. Using HIV-based vaccines, we have protected mice against influenza. We have more work to do to make sure this system is absolutely safe to use on humans but we are quite sure we can do that. We also have to find ways to make large amounts of these vaccine viruses so that they could be used clinically. We need to scale up.
Do you see this primarily as a new way to vaccinate against flu or do you have other goals?
I do have other goals. I think HIV could be used not just as a standard vaccine that prevents infections but as a therapeutic vaccine that treats people after they have become infected – individuals with diseases like hepatitis B and C, for example.
And, of course, there is the ultimate goal of using the virus as a therapeutic vaccine against HIV itself. Instead of putting flu virus proteins into your vaccine you will actually put back a few pieces of the original HIV virus proteins. You will have created a vaccine that could be used to treat Aids. Essentially, we are trying to tame this virus and turn it on itself. There is something very satisfying in that thought.
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