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Natural killer ( NK) cells are essential components of the immune system, and due to their rapid response potential, can have a great impact during early anti-viral immune responses. We have previously shown that interleukin-2-dependent NK and CD4+ T-cell co-operative immune responses exist in long-term simian immunodeficiency virus ( SIV) -infected controlling macaques and can be rescued in SIV-infected non-controlling macaques by a short course of antiretroviral therapy ( ART). Given that co-operative responses may play an important role in disease prevention and therapeutic treatment, in the present study we sought to determine if these responses can be enhanced in chronically SIV-infected macaques by vaccination with a single-dose of envelope protein given during ART. To this end, we treated 14 chronically SIV-infected macaques with ART for 11 weeks and gave 10 of these macaques a single intramuscular dose of SIV gp120 at week 9 of treatment. ART significantly decreased plasma and mucosal viral loads, increased the numbers of circulating CD4+ T cells in all macaques, and increased T-cell-dependent envelope- and gag-specific interferon- γ and tumour necrosis factor- α production by circulatory CD56+ NK cells. The therapeutic envelope immunization resulted in higher envelope-specific responses compared with those in macaques that received ART only. Functional T-cell responses restored by ART and therapeutic Env immunization were correlated with transiently reduced plasma viraemia levels following ART release. Collectively our results indicate that SIV-specific T-cell-dependent NK cell responses can be efficiently rescued by ART in chronically SIV-infected macaques and that therapeutic immunization may be beneficial in previously vaccinated individuals. [ABSTRACT FROM AUTHOR]

Background To increase the immunosurveillance in HIV infection, we used retroviral vectors expressing CD4-chimeric antigen receptors ( CARs) to genetically modify autologous T cells and redirect CTL toward HIV. The CD4 extracellular domain targets envelope and the intracellular signaling domains activate T cells. The maC46 fusion inhibitor binds HIV and blocks viral replication. Methods We stimulated rhesus PBMCs with antibodies to CD3/CD28 and cotransduced T cells with CD4- CAR and maC46 vectors. CD4- CAR-transduced T cells were added to Env+ 293T cells at E:T of 1:1. Killing of target cells was measured as reduced impedance. Results We observed gene expression in 60-70% of rhesus CD3+ CD8+ T cells with the individual vectors and in 35% of the cells with both vectors. CD4- CAR-transduced populations specifically killed Env+ cells. Conclusions In these studies, we showed that designer T cells were redirected to kill Env+ cells. Control of viremia without HAART would revolutionize treatment for HIV patients. [ABSTRACT FROM AUTHOR]