Research in people who have controlled HIV at very low levels for years without drugs has revealed that a human genetic trait linked to autoimmunity may point the way to an effective vaccine against HIV, researchers from Boston report today in the online edition of the journal Nature.
A very small proportion of people (around 0.5%) who become infected with HIV experience little or no disease progression, and maintain a viral load that is near to undetectable for many years.
Scientists led by Professor Bruce Walker of Massachusetts General Hospital have been recruiting these 'elite controllers' of HIV for the past four years with the aim of studying how their immune systems control HIV.
The newly-published study looked at one common feature of many 'elite controllers', a genetic mutation called HLA B57, which is also associated with autoimmune conditions in which immune cells can attack the host’s own proteins because they are not recognised as 'self'.
This study found that people with the HLA B57 gene were more likely to generate killer T-cells which could react to several different HIV proteins, or epitopes. This means that even if one epitope mutates to escape the virus, the killer T-cell can still bind strongly to other viral epitopes, increasing the chance that the virus will be eliminated.
The HLA B57 gene appears to confer this advantage through less rigourous screening of 'self'-reactive T-cells in the thymus, the organ through which they pass in order to become mature T-cells.
They are less likely to be tested against 'self' proteins in the thymus, and so even if 'self'-reactive, less likely to be weeded out at this stage.
Once in circulation, they have a stronger ability to bind to HIV proteins
The finding offers hope that researchers could design a vaccine to help draw out cross-reactive T-cells in people who don’t have the HLA B57 gene. “It’s not that they don’t have cross-reactive T-cells,” said Professor Arup Chakraborty of Massachusetts Institute of Technology, “they do have them, but they’re much rarer, and we think they might be coaxed into action with the right vaccine.”
Kosmrlj A et al. Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection. Nature (advance online publication, May 5, 2010).