[Research Articles] A live-attenuated RhCMV/SIV vaccine shows long-term efficacy against heterologous SIV challenge

Previous studies have established that strain 68-1–derived rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) proteins (RhCMV/SIV) are able to elicit and maintain cellular immune responses that provide protection against mucosal challenge of highly pathogenic SIV in rhesus monkeys (RMs). However, these efficacious RhCMV/SIV vectors were replication and spread competent and therefore have the potential to cause disease in immunocompromised subjects. To develop a safer CMV-based vaccine for clinical use, we attenuated 68-1 RhCMV/SIV vectors by deletion of the Rh110 gene encoding the pp71 tegument protein (Rh110), allowing for suppression of lytic gene expression. Rh110 RhCMV/SIV vectors are highly spread deficient in vivo (~1000-fold compared to the parent vector) yet are still able to superinfect RhCMV+ RMs and generate high-frequency effector-memory–biased T cell responses. Here, we demonstrate that Rh110 68-1 RhCMV/SIV–expressing homologous or heterologous SIV antigens are highly efficacious against intravaginal (IVag) SIVmac239 challenge, providing control and progressive clearance of SIV infection in 59% of vaccinated RMs. Moreover, among 12 Rh110 RhCMV/SIV–vaccinated RMs that controlled and progressively cleared an initial SIV challenge, 9 were able to stringently control a second SIV challenge ~3 years after last vaccination, demonstrating the durability of this vaccine. Thus, Rh110 RhCMV/SIV vectors have a safet...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research