Antibody-based vaccine for HIV

02 December 2011
Posted by Chris Smith.

A modified virus encoding an anti-AIDS antibody can protect animalsHIV-1 particles assembling at the surface of an infected macrophage. from HIV infection.

An estimated 7000 new cases of HIV occur each day, the majority of them in developing countries where access to heathcare and antiretroviral drugs is limited. For this reason, a vaccine is urgently needed to control the spread of the infection.

Previous vaccine strategies have performed poorly, barely making a dent in infection rates, and so far the only intervention with proven longterm efficacy has been circumcision, which reduces a man's risk of acquiring the disease by 60-80%.

But a paper published this week in Nature by Caltech scientist David Baltimore and his colleagues might hint at a new way to combat the problem. They've used a self-complementary adeno-associated virus 8 (scAAV-8) as a vector, to ferry into experimental animals the DNA code for an antibody called b-12, which has HIV-neutralising properties.

This antibody, discovered some years ago, is special because it has the capacity to disable many different strains of HIV and can prevent infection becoming established in the first place.

The Caltech team injected 100 billion particles of the scAAV-8 vector into the leg muscles of experimental mice. These animals had also been modified to carry in their bloodstreams the human CD4 white cells targeted by HIV.

Within a week, high levels of the human b-12 antibody were detectable in the blood of the mice and expression was sustained for at least one year, which was the duration of the experiment.

The researchers then challenged the animals with an injection of HIV sufficiently large to infect the vast majority of unvaccinated mice and tracked the numbers of CD4 cells circulating in the bloodstream.

Compared with control mice, in which the CD4 count dropped nearly to zero, the b-12 antibody-producing animals showed complete protection against the infection.

The result is stunning, but not without a few residual wrinkles that need ironing out. This is a study in mice and so the concept would need to be proven in humans. Also, the long-term tolerability and safety of sc-AAV vectors and the effect of sustained high-level expression of the b-12 antibody are unknown, and it's unclear how much of the viral vector would be required to protect larger species including humans.

However, according to the team, who dub their technique "VIP" - vectored immunoprophylaxis - "given the level of protection that VIP has demonstrated in vivo, we believe that highly effective prophylaxis through expression of existing monoclonal antibodies against HIV in humans is achievable."

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