Previous studies have found that strain 68-1-derived rhesus cytomegalovirus (RhCMV) vectors that express simian immunodeficiency virus (SIV) proteins (RhCMV/SIV) can elicit and maintain protective cellular immune responses in rhesus monkeys (RMs). However, these RhCMV/SIV vectors were replication and spread competent and therefore could cause disease in immunosuppressed patients. The authors attenuated 68-1 RhCMV/SIV vectors by deleting the Rh110 gene encoding the pp71 tegument protein (ΔRh110), which allows for the suppression of lytic gene expression. ΔRh110 RhCMV/SIV vectors were found to be highly spread deficient in vivo (1000-fold compared to the parent vector) but can still superinfect RhCMV+ RMs and generate high-frequency effector-memory-biased T cell responses. The authors found that ΔRh110 68-1 RhCMV/SIV-expressing homologous or heterologous SIV antigens were still highly efficacious against intravaginal (IVag) SIVmac239 challenge, leading to control and clearance of SIV infection in 59% of vaccinated RMs. In addition, of 12 ΔRh110 RhCMV/SIV-vaccinated RMs that cleared an initial SIV challenge, nine were able to stringently control a second SIV challenge 3 years after the last vaccination, demonstrating that this vaccine is durable. Therefore, ΔRh110 RhCMV/SIV vectors have a good safety and efficacy profile.
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