HIV vaccine failure probably caused by adenovirus

The recent failure of an HIV vaccine was probably caused by the immune system reacting to the virus ‘shell’ used to transmit the therapy around the body, revealed by researchers.

The new srudy is published in the Proceedings of the National Academy of Sciences.

The trial, called ‘STEP’, was halted in September 2007 because preliminary results suggested that people who had been given the vaccine were more likely to be infected with HIV than people who had been given a placebo.

The researchers from Imperial College London, King’s College London and Royal Holloway, University of London, say their findings mean scientists may have to rethink other vaccines they are developing for diseases like HIV, tuberculosis and malaria, which are delivered in the same way, using the same virus ‘shell’.

The vaccine used an adenovirus, which normally causes the common cold, to enable the vaccine therapy to travel around the body. Harmless HIV genes were then inserted into the virus. It was thought that this would help the immune system to learn to recognise and fight off HIV.

This study suggests that after receiving the trial vaccination, people who had previously built up immunity to the adenovirus had an influx of immune cells called CD4 T-cells homing in on their mucous membranes, as these cells prepared to fight off a new adenovirus infection. Mucous membranes are found in areas including the nose, mouth, vagina and gut. HIV naturally infects CD4 T-cells, so this inadvertently provided HIV with an abundance of potential new homes at the sites where the virus would naturally enter the body during sexual intercourse, thereby increasing people’s risk of infection.

The researchers say their findings are a warning for scientists developing adenovirus vaccines against other diseases, as the same effect occurs with other, perhaps all, adenovirus subtypes.

Adenovirus infection is common and there are 51 known human strains. Around half of all adults in the developed world and about 90 percent of individuals in sub-Saharan Africa, where HIV is most prevalent, have built up immunity to the subtype of adenovirus used in STEP.

Preliminary results of the vaccine trial showed that people who had previously been infected with the adenovirus used in the trial had a significantly higher risk of being infected with HIV following the vaccine compared to people who were given a placebo.

Source: Imperial College London, UK



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