Hiding cells to prevent HIV transmission
The fight against HIV is ongoing and despite our rapid progression against the disease we still lack a cure or even adequate treatment for people infected. However, new research suggests that cloaking immune cells with antibodies that block T cell trafficking to the gut can substantially reduce the risk of viral transmission, at least in a non-human primate model of HIV infection. If it works out, this could help slow down the spread of HIV and give people a better shot at a normal life.
The findings suggest that drugs that are already in clinical trials for inflammatory bowel diseases might actually be effective in the treatment or prevention of HIV infection.
“We were surprised by the effects that we observed,” says senior author Aftab Ansari, PhD.
“Our goal was to demonstrate that blocking CD4+ T cell trafficking to gut tissues could decrease the level of virus in the gut and help mount an effective immune response, but we found that administration of the antibody could actually prevent transmission.”
“The results of this study suggest that this form of therapy could counteract pathologies that lead to gastrointestinal symptoms and poor outcomes in HIV infection. Exploration of how this could be combined with anti-retroviral drug regimens is warranted.”
CD4+ T cells found in the gut are key early targets during HIV infection and their depletion is a harbinger of disease progression. Researchers were able to “mask” these cells by using an antibody against α4β7 integrin, a molecule that promotes these T cells’ homing to gut-associated lymphoid tissues.
The antibody does not eliminate the T cells, but it prevents them from homing to the gut and also blocks their interaction with infectious virus.
A previous study of anti-α4β7 treatment in acute SIV infection found that it could not only suppress viral load, but also keep treated animals healthy for years, while control animals’ SIV infection progressed to AIDS.
In the report, researchers examined the effect of targeting α4β7 in a model where female rhesus macaques were repeatedly challenged once per week with HIV’s cousin SIV intravaginally.
Ten out of 12 control animals became infected. In contrast, only one out of 12 α4β7-antibody-treated animals became infected by week five. Five more became infected by week eight, and six of twelve remained uninfected. The researchers calculated that anti-α4β7 treatment leads to a 2.7 fold decreased risk per challenge.
The researchers also observed a decrease in the level of virus in gut tissues and the presence of residual virus in cervical tissues in alpha-4-beta-7-antibody-treated animals. They interpret this as indicating that viral transport away from the point of infection is inhibited
“Masking α4β7 integrin may be preventing transmission by suppressing the spread of a nascent genital infection to the gut, where large numbers of vulnerable T cells reside,” Ansari says.
Hopefully the team will be able to start human trials soon, since the risks of using the drugs outweigh any sort of side effects they could have, all while (hopefully) improving the quality of life of the person using them. Of course, as the case with anything that needs to be proven to work, it will probably be more than just a few years before you will see these drugs being uses as treatment options.
Byrareddy, S., Kallam, B., Arthos, J., Cicala, C., Nawaz, F., Hiatt, J., Kersh, E., McNicholl, J., Hanson, D., Reimann, K., Brameier, M., Walter, L., Rogers, K., Mayne, A., Dunbar, P., Villinger, T., Little, D., Parslow, T., Santangelo, P., Villinger, F., Fauci, A., & Ansari, A. (2014). Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection Nature Medicine DOI: 10.1038/nm.3715