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HIV discovery brings vaccine closer

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HIV virusAn investigation into the activity of antibodies in HIV patients has revealed that the HIV virus can mutate in order to ‘escape’ this immune response.

Human ADCC (antibody-dependent cell-mediated cytotoxicity) antibodies – which are often present in high concentrations in HIV-infected patients – have been strongly implicated in the protection from HIV in several vaccine trials.

However, we still do not how these antibodies really work, and researchers hope that a better understanding of their processes could lead to HIV treatments that work by boosting the antibodies’ defences.

“These results show what a slippery customer the HIV virus is, but also shows that these ADCC antibodies are really forcing the virus into changing, in ways that cause it to be weaker,” said lead author Stephen Kent from the University of Melbourne in Australia.

Pinpointing mutation’s location

The term ADCC describes an immune phenomenon whereby antibodies bind to cells infected with a virus. This process activates ‘natural killer cells’ that then attack virus-infected cells.

These natural killer cells destroy infected cells by releasing cytokines, such as interferon-gamma, which are small cell-signalling protein molecules that are secreted by numerous immune system cells and cells in the nervous system.

To investigate further, the researchers analysed blood samples of HIV patients to find where the ADCC antibodies were attacking the virus. They did this by using a staining technique to detect exactly which parts of the virus – that is, which peptide segments – were stimulating the release of cytokines.

Stopping the virus taking hold

The team sequenced the patient’s own virus and found mutations at sites targeted by these ADCC antibodies. Their technique also allowed them to study how the mutations arose over time.

The assay proved additionally valuable because it can be performed on serum or plasma samples, and not cells, which makes for a much easier and less invasive procedure where patients are concerned.

The results, published in Proceedings of the National Academy of Sciencestis month, show that ADCC antibodies force the virus into changing in ways that cause it to be weaker, said Kent.

“They also imply that if good ADCC antibodies were available prior to infection, via a vaccine, we might be able to stop the virus taking hold. This is the holy grail.”

According to co-author Ivan Stratov from the University of Melbourne, “The potential to use ADCC antibodies to kill virus infected cells (rather than just free virions) is a great advance in HIV vaccine research. And harnessing natural killer cells to combat HIV could add great potency to existing vaccine strategies.”

The team is now working on purifying and producing these antibodies in bulk quantities and testing them in a simian (primate) infection model to see if they can prevent infection – by the simian immunodeficiency virus – in monkeys.

Putting pressure on the virus

Over 40 million people around the world have acquired HIV or AIDS, according to the latest toll compiled by the World Health Organisation (WHO) and UNAIDS.

Although the disease was identified over 25 years ago, there is still no vaccine or cure but antiretroviral drugs can be used to manage the condition.

“The work … shows that these types of antibodies are initially quite effective in eliminating virus but eventually they fail because the virus mutates too quickly,” said Marc Pellegrin from the Walter & Eliza Hall Institute of Medical Research in Melbourne, who was not involved in the study.

“The implications … are that our immune system, through these antibodies, is able to exert considerable pressure on the virus to the point where it must mutate to persist and survive. The corollary is that if we can boost this type of response and make it more robust and broad we can better control HIV.”

Via CosmoMag

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One Response

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  1. The re:solve AIDS project is raising money to get a promising AIDS vaccine through human testing so that it can be produced and made available to everyone who needs it. http://bit.ly/e4ehI7

    Jeff

    May 26, 2011 at 9:07 pm


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