CMV-vectored vaccines expressing SIV antigens have mediated unprecedented levels of virus control following SIV challenge in rhesus macaques. Remarkably, protection was dependent on nonclassically restricted CD8+ T cells. Here, we review the latest research in CMV-vectored vaccines in both humans and nonhuman primates as well as recent advances in the understanding nonclassically restricted T cells, particularly MHC-E-restricted CD8+ T cells.
Recent studies have investigated human translation of CMV-vectored vaccines including studies to ensure vaccine vector safety. Other work has focused on testing of animal models to investigate the relative contribution of MHC diversity and CMV strain on T-cell induction. Lastly, several groups have investigated MHC-E peptide binding, including HLA-E, have found that MHC-E can accommodate different peptide motifs, consistent with the original observations in CMV-vaccinated macaques.
CMV remains a promising vaccine vector with the potential to be protective against multiple diseases, including HIV. However, CMV is highly species-specific and in humans, congenital infection can lead to serious birth defects. To ensure safe translation to humans, further clinical and animal studies are needed to better understand CMV-vectored immunity as well as more basic immunological questions relating to the induction of classical vs. nonclassical T cells.
aUNC HIV Cure Center
bDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Correspondence to Nilu Goonetilleke, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, 2023 Genetic Medicine Building, CB#7042, 120 Mason Farm Road, Chapel Hill, NC 27599-7435, USA. Tel: +1 919 962 3129; e-mail: firstname.lastname@example.org