Thursday, December 1, 2011

Muscle-powered therapy can prevent HIV infection

One of the body's protection mechanisms against infection is churning out antibodies that bind to pathogens, which are consequently rendered immobile, or flagged to be killed by immune cells. But HIV is different. Because the virus infects certain immune cells, the immune response is hampered, which includes the antibody production. Scientists have artificially made a bunch of antibodies able to bind HIV, but the cells that are supposed to produce those antibodies, are impaired in AIDS patients. As an alternative, a gene-based therapy was developed to modify other cells to start making antibodies. As it turns out, muscles, that have the required genes built in, were able to make antibodies that protect against HIV infection, even after the virus is trying to destroy the immune system during an infection. That is a promising result in developing a vaccine that eradicates HIV, and consequently AIDS as a disease.

Gene therapy
The therapy, developed by the California Institute of Technology, works by genetically modifying muscle cells. Oddly enough, to protect us from a virus, they want to infect us with a virus. Using the common cold virus, which has been rendered incapable of doing something harmful, the scientists were able to modify muscle cells in the hind leg of mice, which served as the injection site. The injected viruses had been modified to contain antibody genes that function as the blueprint for the actual antibodies that bind and neutralize HIV.  While it is not their job, the muscle cells started producing antibodies, something that is normally only performed by highly specialized immune cells.

Protection from HIV
Mice that were set to produce HIV antibodies appeared to be functional. After infection, the scientists tried to get the mice infected with HIV, but the virus did not seem to be successful. Even after they were injected with a 100-fold higher concentration of HIV than normally used for infection. This indicates muscle can continue to produce neutralizing antibodies after the virus tries to shut down the immune system. It is interesting to note that a single injection causes lifelong expression of the required antibodies to combat HIV.

Normally, vaccines work by priming the immune system towards a pathogen. By infecting people with parts of a pathogen, or characteristic proteins, our immune cells will generate a response and consequently make memory cells. In the immune system, memory cells play an important role in remembering how to fight a pathogen. When it infects us for the second time, the memory cells make it possible to launch a much faster and much stronger attack. That is why you only get certain diseases once. Vaccines work with the same principle. After infection with something that is mimicking a micro-organism, but does not cause disease, the immune system will know what to do when the real deal tries to invade our body.

Developing a HIV vaccine
HIV vaccines are a different story. Because the virus attacks the immune system head on, the cells that actually need to launch an attack are impaired due to the infection. While it could be eradicated before it can be harmful, HIV has a few tricks up its sleeve to prevent that. The immune system recognizes certain molecular patterns, which can for example be part of a protein present on the outer layer of the virus. By changing its outer appearance, the immune system is no longer able to find the molecular patterns it was primed for. HIV therefore escapes the memory response and is able to impair the immune system before it has recognized the new version and launch an effective attack. Therefore it was necessary to find an alternative target to produce the necessary antibodies to prevent HIV from infecting immune cells.

HIV infection and AIDS
HIV is special in the sense that it specifically attacks immune cells. To be precise, it infects CD4+ T lymphocytes, which are commonly known as T helper cells. They obtained the name because they have a supporting role in generating an immune response. They activate the so-called B cells to start churning out antibodies, and stimulate other T cells, dubbed CD8+, to start killing infected cells. Without them, the body can not launch a proper immune response, which is exactly what the problem is when HIV infection has progressed to cause the disease AIDS. Eventually, patients die from secondary infections that the body is no longer able to fight off.

The present study has been performed in mice. As always, human testing is needed before proclaiming we can cure AIDS. However, the results are very promising, and if we can prevent an infection in humans to produce the symptoms of AIDS, as seems possible in mice, we might not have to worry about HIV infections anymore.

Because of the consequences HIV can have on our health, it is subject to a lot of research. There are many other initiatives to develop a functioning vaccine. One of them focuses on a molecule that the virus uses to enter the cell. By making antibodies against it, HIV could be prevented to enter the cell and thus not cause any harm. These antibodies are derived from the same family as the one in the aforementioned muscle-based study. Oddly enough, a certain research group uses fluorescent glowing cats to study HIV prevention.
Schematic of how HIV enters a T cell.

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