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Innovative gene therapy protects mice from HIV infection

05 December 2011

By Dr Tamara Hirsch

Appeared in BioNews 636

US scientists have induced long-lasting human immunodeficiency virus (HIV) protection in mice from a single injection. Their study, published in the journal Nature, uses gene therapy to stimulate production of antibodies against the virus. It may bring us a step closer to protecting humans against HIV infection.

Nobel laureate Dr David Baltimore and his team at the California Institute of Technology isolated a stretch of DNA coding for antibodies which neutralise the virus from the blood of HIV patients. This DNA was inserted into a harmless virus called an adenovirus which, when injected into the mice, is able to deliver the DNA into cells. This procedure is called Vectored ImmunoProphylaxis (VIP).

Attempts to develop a vaccine against HIV have so far been unsuccessful mainly because the virus seems able to evade recognition by the immune system. As Dr Alejandro Balazs, lead author of the study and a postdoctoral scholar in Dr Baltimore's lab, explains: 'VIP has a similar effect to a vaccine, but without ever calling on the immune system to do any of the work. Normally, you put an antigen [...] into the body, and the immune system figures out how to make an antibody against it. We've taken that whole part out of the equation'.

After the DNA-carrying adenovirus has been injected into leg muscle, the DNA is incorporated into the muscle cells' genome where it programs the cells to manufacture and secrete the HIV antibody into the bloodstream. The mice in the study produced enough of the neutralising antibody that they were protected against HIV infection. Even when the exposure to HIV was increased over 100-fold the mice still mounted a successful response.

Five different neutralising antibodies were individually tested and two of these, b12 and VRC01, proved completely protective. The mice used were engineered to carry human immune cells as normal mice are not susceptible to HIV.

VIP is a platform technique, meaning that as other neutralising antibodies are identified for HIV or other infectious diseases, they can also be delivered using this method.

The current study builds on work by scientists at the Children's Hospital of Philadelphia in Pennsylvania, who in 2009 first described the effectiveness of VIP in preventing transmission of simian immunodeficiency virus - the monkey-specific version of HIV – in monkeys.

'If humans are like mice, then we have devised a way to protect against the transmission of HIV from person to person', said Dr Baltimore. 'But that is a huge if, and so the next step is to try to find out whether humans behave like mice'. Dr Baltimore's team are planning to test the safety and efficacy of VIP in clinical trials.

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