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Effective HIV vaccine comes closer to reality !

The new findings point the way towards a potentially more effective vaccine that would generate V1V2-directed HIV neutralising antibodies.WASHINGTON: Scientists have discovered how the immune system makes a powerful antibody that blocks HIV infection of cells by targeting a key site, paving way for an effective vaccine for the deadly virus.

Researchers believe that if a vaccine could elicit potent antibodies to a specific conserved site in the V1V2 region of the virus, one of a handful of sites that remains constant on the fast-mutating virus, then the vaccine could protect people from HIV infection.

Analyses of the results of a clinical trial of the only experimental HIV vaccine to date to have modest success in people suggest that antibodies to sites within V1V2 were protective.

The new findings point the way towards a potentially more effective vaccine that would generate V1V2-directed HIV neutralising antibodies, researchers said.

The study led by the National Institute of Allergy and Infectious Diseases ( NIAID) scientists began by identifying an HIV-infected volunteer who naturally developed V1V2-directed HIV neutralising antibodies, named CAP256-VRC26, after several months of infection.

Using techniques similar to those employed in an earlier study of HIV-antibody co-evolution, the researchers analysed blood samples donated by the volunteer between 15 weeks and 4 years after becoming infected.

This enabled the scientists to determine the genetic make-up of the original form of the antibody; to identify and define the structures of a number of the intermediate forms taken as the antibody mutated towards its fullest breadth and potency.

It also allowed them to describe the interplay between virus and antibody that fostered the maturation of CAP256-VRC26 to its final, most powerful HIV-fighting form.
The study showed that after relatively few mutations, even the early intermediates of CAP256-VRC26 can neutralise a significant proportion of known HIV strains.

This improves the chances that a V1V2-directed HIV vaccine developed based on the new findings would be effective, according to scientists, who have begun work on a set of vaccine components designed to elicit V1V2 neutralising antibodies and guide their maturation.

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Effective HIV vaccine comes closer to reality

The researchers discovered that certain amino acids located on the gp120 protein undergo a process that stabilises the trimer in its closed position. ReutersScientists have discovered a mechanism that helps HIV evade antibodies and stabilise key proteins, a finding that could pave way for more effective vaccine for the deadly virus.

National Institutes of Health (NIH) scientists found the mechanism involved in stabilising key HIV proteins and thereby concealing sites where some of the most powerful HIV neutralising antibodies bind.

Numerous spikes jut out of the surface of HIV, each containing a set of three identical, bulb-shaped proteins called gp120 that can be closed together or spread apart like the petals of a flower, researchers said.

Some of the most important sites targeted by HIV neutralising antibodies are hidden when the three gp120s, or the trimer, are closed, and the gp120 trimer remains closed until the virus binds to a cell, they said.

The researchers discovered that certain amino acids located on the gp120 protein undergo a process that stabilises the trimer in its closed position.

In this process, called sulfation, the amino acids acquire a sulfur atom surrounded by four oxygen atoms.

By either blocking or increasing sulfation of these amino acids, the researchers changed the sensitivity of the virus to different neutralising antibodies, indicating that the trimer was being either opened or closed.

The scientists suggest that if the synthesised gp120 widely used in HIV research were fully sulfated during manufacture, the resulting product would adopt a more true-to-life structure and more closely mirror the way the immune system sees unbound HIV.

This might help generate a more effective HIV vaccine, NIH researchers said.

They added that full sulfation of gp120 may enable scientists to crystallise the molecule more readily, which also could advance HIV vaccine design.

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