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Explanations for HIV vaccine failure
Maxine Clarke
Friday, 07 November 2008 11:09 UTC
A report in Nature online news this week (5 November 2008) looks at possible explanations for an HIV vaccine failure. The suggestion is that the experimental vaccine against AIDS might have failed in part because it made some people’s immune cells more vulnerable to HIV infection.
Eric Kremer and colleagues examined why people participating in the STEP vaccine trial who had previously been exposed to a cold virus, adenovirus 5, seemed more likely to become infected with HIV-1 than those who hadn’t been exposed to the virus (see HIV vaccine may raise risk). The trial was halted last September.
Kremer and his colleagues found that when antibodies to adenovirus 5 were combined with the vaccine backbone in a culture dish, they triggered a pathway that causes the activation of T cells, which are targeted by HIV in their active state. In cell culture, T cells succumbed to HIV-1 infection three times more quickly than did those in a mixture that lacked adenovirus 5 antibodies. The researchers suggest that injecting an adenovirus-5-based vaccine into people with adenovirus 5 antibodies could have created a “chronic permissive environment for HIV-1 infection”.
The findings, explains Warner Greene, the director of the Gladstone Institute of Virology and Immunology in San Francisco, who was not involved in the work, suggest that HIV-1 “encounters a singularly target-rich environment favouring successful HIV transmission” in people who have previous exposure to adenovirus 5.
But many researchers are yet to be convinced that the new work explains what went wrong in the original trial. All of the group’s experiments were done in culture dishes, and did not use cells or antibodies taken from individuals who were actually involved in the STEP trial.
For futher details, see the Nature News story.
Updated 07 November 2008 11:12 UTC
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Replies
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A couple of days after writing this post, a paper in Nature Medicine caused a stir: see this Great Beyond blog post and associated links
From the post: ‘scientists from the US and UK report making T cells that bind to the HIV-1 strain of the virus 450 times more strongly than natural T cells…….A number of news sources says these ‘bionic assassins’ are to be “sent on a search-and-destroy mission against [the] HIV virus’? Alternatively, ‘pimped up T-cells’ are off to ‘seek out and destroy HIV’?
Well, leaving aside the RAS syndrome in the first one they don’t really ‘search’ for HIV, they attack it if they bump into it, so this isn’t really right.
These may be ‘souped-up immune cells’, they may be ‘assassin cells’, but sadly the image of them relentlessly hunting down HIV is a little far fetched.’ -
Too high a binding affinity always leaves me uneasy. What is there to prevent false positives? Antigen-immune receptor interactions, amongst all receptor-ligand type of interactions, may often be dependent upon the three-dimensional conformation of the epitope on the antigen. Similarity of this 3D-conformation is cited as responsible for the vast majority of cross-reactive antibodies seen in people’s serum, that recognize polysaccharide antigens from a diverse group of pathogens. What if the admittedly ‘supraphysiologic’ TCR recognizes more than just the immunodominant HIV peptide?
The mention of the RAS syndrome brought a chuckle!!
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“What is there to prevent false positives?”
Not much as far as I know. What is there to distinguish a false positive from a real one?
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