In vitro SIV replication kinetics correlate with vaccine induced cellular immune responses and predict post-challenge outcome in immunized rhesus macaques

Strong and sustained immune response is central in AIDS vaccine research. Here, we use an in vitro model to describe correlation kinetics of virus replication and T-cell responses. Eighteen rhesus monkeys were recruited into Group-1 (controls) and groups 2 and 3 which were DNA-primed followed by adenovirus-vaccine boost via different routes. All animals were challenged with SIVmac239 after 44 weeks. During immunization, ex-vivo interferon gamma (IFN-γ) responses and in vitro SIV suppressor activities (VSA) in cell-culture were determined respectively using ELISPOT and a non-cytotoxic antiviral activity assay. Virus replication efficiency in vitro (VVR) and after challenge was measured using real-time PCR. At baseline, VVR was comparable in all groups and remained constant in controls. However, VVR declined significantly (p = 0.001) in vaccines, correlated with increased IFN-γ responses (p = 0.019) and VSA (p = 0.05). Peak viremia post-challenge was significantly lowered in vaccinnes (p = 0.006) and correlated with in vitro kinetics for control animals. Acute-phase set point correlated with VSA (p = 0.001) but not IFN-γ levels. Our in vitro model predicts post-challenge outcome and implicates multifactorial cellular immune factors in controlling viral replication. Optimizing these immune components in candidate vaccine designs may improve potency and outcome.