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U of M researchers develop vaccine that can kill a model AIDS virus in mice

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The elusive HIV/AIDS vaccine. Researchers have been trying to develop this vital preventive tool for the viral syndrome for years.

Now, researchers at the University of Miami Miller School of Medicine, Center for AIDS Research, have developed a vaccine that generates an immune system response strong enough to kill a model AIDS virus in mice.

The study was recently published in the American Society for Microbiology's (ASM) Journal of Virology last month.

The research team led by Geoffrey W. Stone, Ph.D., assistant professor of microbiology and immunology, report the vaccine, when targeted to a unique receptor in the immune system, can generate unprecedented T cell responses to HIV. The receptor involved is called CD40, and the vaccine uses a special form of its natural binding protein, CD40 ligand (CD40L), to enable important immune cells called dendritic cells to detect the presence of HIV proteins.

According to a U of M news release:

Dendritic cells are the gatekeepers of the immune system. They collect and process foreign proteins, known as antigens, and then alert the rest of the immune system to the invader. An essential step in this process is that the dendritic cells must become activated through the CD40 receptor.

Stone and his collaborators have found that directly coupling the foreign protein antigen to a special form of CD40 ligand leads to extraordinarily strong CD8+ T cell responses in mice. In the case of an HIV protein, the vaccinated mice were able to completely fend off infection by more than 10 million model viruses containing the HIV protein antigen. This type of extreme immune protection, called sterilizing immunity, is rarely seen in vaccine studies.

The Miami Herald reports Dr. Stone as saying, “We’re trying to get a magic bullet that can bring information about HIV to dendritic cells.”

“The key to the vaccine’s effectiveness is that it contains a new form of CD40 ligand connected to the foreign protein antigen,” explained Stone. “This means that the dendritic cell both receives the antigen and is activated by its CD40 receptor at the same time.”
Dr. Stone said the vaccine is in the very early stages of development; however, the results thus far have been dramatic.

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“Vaccine-induced protection has been very difficult to achieve,” said Stone. “This new vaccine design takes us to another level in stimulating the immune system to produce CD8+ T cells. The next steps will be to test the vaccine in monkeys, and then in humans.”

In addition, the school reports that these recent advancements may lead to the development of additional new vaccines for influenza, malaria and cancer.

This research from the Miller School's Center for AIDS Research follows the finding of a study in the Journal of Immunology published nearly one year ago where a vaccine developed with a novel heat-shock technology provided significant protection against the Simian Immunodeficiency Virus (SIV), a non-human virus closely related to the HIV virus that causes AIDS.

The human immunodeficiency virus (HIV) is a virus spread through body fluids that affects specific cells of the immune system, called CD4 cells, or T cells. Over time, HIV can destroy so many of these cells that the body can’t fight off infections and disease. When this happens, HIV infection leads to AIDS.

Although there is currently no cure or preventive vaccine against HIV, antiretroviral therapy (ART) can dramatically prolong the lives of many people infected with HIV and lower their chance of infecting others.

According to AIDS.gov, in the US, the Centers for Disease Control and Prevention (CDC) estimates that 1,144,500 persons aged 13 years and older are living with HIV infection, including 180,900 (15.8%) who are unaware of their infection. Over the past decade, the number of people living with HIV has increased, while the annual number of new HIV infections has remained relatively stable. Still, the pace of new infections continues at far too high a level— particularly among certain groups.

Globally there are 33.4 million people currently living with HIV/AIDS.

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