New evidence in the HIV immune response

03 November 2010

HIV can be partially contained by the immune system of the infected patient, but researchers are still unravelling exactly how this happens. A unique interdisciplinary team brought together by the Oxford Martin School and Imperial College London have unlocked another piece in this puzzle, after having a rare opportunity to investigate the role of the blood’s B-cells in HIV suppression. Their research, published this week in Nature Communications, indicates that these cells may be more important in controlling chronic HIV infection than previously suspected.

HIV vaccine research has so far focused on another type of blood cell, the T-cell, as there has long been evidence that these cells play a part in HIV suppression. However, due to the virus’s ability to evolve and mutate rapidly, progress on vaccines has been slow. But the role of B-cells in the control of HIV is still poorly understood, and a clearer picture of the body’s immune response could help researchers develop new approaches to HIV prevention and management.

B-cells produce neutralising antibodies that attack foreign invaders. Some individuals possess antibodies that appear to be very potent when it comes to HIV, but isolating the impact of B-cells within the body’s whole immune response has been difficult. Scientists have manipulated cell counts in animals, but these types of studies are not feasible in humans, nor do they provide the kind of concrete evidence needed to design human vaccines. The team from the Oxford Martin School and Imperial College were able to examine the effect B-cells have on HIV viral load with a human patient whose B-cell count had been depleted due to a second, unrelated condition.

HIV infection is usually treated with antiretroviral therapy to bring the viral load under control. Upon his diagnosis, this patient was given a short course of highly active antiretrovirals, after which his viral load was low and considered stable. Three years earlier, the patient had also been diagnosed with lymphoma, a blood cancer of the B-cells, but the disease was low-grade and was not treated at the time. About two and half years after his HIV diagnosis, and after he had finished the antiretroviral therapy that had stabilised his viral load, the patient experienced a rise in blood protein that was attributed to his lymphoma. He was started on rituximab, a common chemotherapy drug. Rituximab attacks cancer by destroying the B-cells that might host it, killing off both malignant and normal B-cells indiscriminately. A patient on this type of treatment will have a low B-cell count.

About four weeks after the start of chemotherapy, the patient felt unwell and experienced malaise and fever typical of pronounced HIV infection. As his B-cell count had decreased, his viral load increased. It was brought back under control following the end of the rituximab treatment and another course of antiretrovirals. The team used multiple analytical techniques to determine that the viral load was directly related to the patient’s B-cell count.

This study produced, for the first time in a human subject, clear evidence that the absence of B-cells increases the HIV viral load. In other words, B-cells appear to have a crucial role in containing HIV infection. This evidence may inform the design of future immunotherapies and HIV vaccines.

This study was a partnership of members of the Institute of Emerging Infections at the Oxford Martin School and the Faculty of Medicine at Imperial College London. The team consisted of clinicians, HIV researchers, evolutionary biologists, and specialists in viral evolution.