191 Anti-FasL treatment preserves SIV-specific memory and slows progression to AIDS in rhesus macaques

Abstract

Previously we reported an increased survival advantage in SIV-infected rhesus macaques after injection with a FasL-blocking monoclonal antibody (Salvato et al., Clin Dev Immunol. 2007: 93462). In the present study we analyzed the effect of such FasL blocking on immune parameters and disease progression in a cohort of SIV-infected rhesus macaques. Upon infection, various immune parameters in the blood developed highly significant differences between animals given anti-FasL RNOK203 antibody and those given an isotype control antibody. The anti-FasL treated animals had a clear preservation of central memory CD4 lymphocytes starting from acute infection through at least set point viremia. The total memory CD4 lymphocytes in these animals were also significantly higher throughout the 25-week study period. Anti-FasL treatment resulted in significantly higher percentages of memory CD8 lymphocytes in peripheral blood. Besides these changes in the memory lymphocyte compartment, the treated animals had a higher response to infection as evidenced by increased turnover of CD4 and CD8 lymphocytes expressing Ki67. Importantly, the antigen-specific cellular immune responses were significantly higher at 4, 6 and 17 weeks after infection in anti-FasL treated animals. Preservation of memory lymphocytes and cellular immunity are considered the main correlates of protection in SIV infection. Our study demonstrates that FasL is a major contributor towards depletion of anti-SIV immunity and that blocking this pathway is a beneficial strategy that should be considered for vaccine formulations.