Positive selection of mC46-expressing CD4+ T cells and maintenance of virus specific immunity in a primate AIDS model.

Publication Type:

Journal Article

Source:

Blood (2013)

Keywords:

2013, Clinical Research Division, June 2013

Abstract:

Despite continued progress in the development of novel antiretroviral therapies, it has become increasingly evident that drug-based treatments will not lead to a functional or sterilizing cure for HIV(+)-patients. In 2009, an HIV(+)-patient was effectively cured of HIV following allogeneic transplantation of hematopoietic stem cells (HSCs) from a CCR5(-/-) donor. The utility of this approach, however, is severely limited due to the difficulties in finding matched donors. Hence, we studied the potential of HIV/SHIV-resistant stem cells in the autologous setting in a nonhuman primate AIDS model and incorporated a fusion inhibitor (mC46) as the means for developing infection-resistant cells. Pigtail macaques underwent identical transplants and SHIV-challenge procedures with the only variation between control and mC46 macaques being the inclusion of a fusion-inhibitor expression cassette. Following SHIV-challenge, mC46 macaques, but not control macaques, showed a positive selection of gene-modified CD4(+) T-cells in peripheral blood, GI tract and lymph nodes accounting for >90% of the total CD4(+) T-cell population. mC46 macaques also maintained high frequencies of SHIV-specific, gene-modified CD4(+) T-cells, an increase in non-modified CD4(+) T-cells, enhanced CTL function and antibody responses. These data suggest that HSC protection may be a potential alternative to conventional antiretroviral therapy in patients with HIV/AIDS.